BG65279B1 - C(7) ester substituted taxanes and their use as antitumor agents - Google Patents

Abstract

The invention relates to taxanes having an ester substituent at C(7), a hydroxy substituent at C(10), and a range of C(2), C(9), C(14), and side chain substituents.

Description

BACKGROUND OF THE INVENTION

The invention relates to novel taxanes that are extremely useful as antitumor agents.

The taxa group of the drawstring family, including baccatin III and taxol, is of considerable interest, both biologically and chemically. Taxol is used as a chemotherapeutic anticancer agent and has a broad spectrum of tumor-inhibiting action. Taxol has a 2′S, 3′S configuration and the following structure formula:

Ace

CeHgCONH Ο \ I 0 ° π SCx / but Yi whereAaseacetyl.

Colin et al. describe in U.S. Pat. No. 4,814,470 that certain taxol analogues have an effect significantly greater than that of taxol. One of these analogues, usually given as docetaxel, has the following structural formula:

Although taxol and docetaxel are useful chemotherapeutic agents, their efficacy is limited, their efficacy against certain types of cancer is limited, and toxicity is observed when taken at different doses. Therefore, there remains a need for additional chemotherapeutic agents with improved efficacy and lower toxicity.

SUMMARY OF THE INVENTION

It is an object of the present invention to compare taxanes with taxol and docetaxel in terms of efficacy as antitumor agents and toxicity. These taxanes have an ester substitute for C-7 other than formate, acetate, and heterosubstituted acetate; hydroxy substituent of C-10 and a number of substituents of C-3 '.

The present invention relates to a taxane composition, in particular, pharmaceutical compositions comprising a taxane and a pharmaceutically acceptable carrier, as well as methods of administration.

Some of the other objects and features of this invention will be apparent, and others will be set forth below.

Description of preferred embodiments of the invention

In one embodiment of the present invention, the taxanes of the present invention have the following structure (1):

where

R ₂ is an acyloxy group;

R 1 represents R ₇ COO-;

R _7a represents a hydrocarbyl group, a substituted hydrocarbyl group or a heterocyclo group, wherein said hydrocarbyl or substituted hydrocarbyl group contains carbon atoms at the alpha and beta positions relative to the carbon atom linking the substituent R _7a ;

R 1 represents a keto group, hydroxy or acyloxy group;

_{R] 0} is hydroxy;

R _{14 is a} hydrido or hydroxy group;

X ₃ represents a substituted or unsubstituted alkyl group, alkenyl group, alkynyl group, phenyl or heterocyclo group;

X ₃ represents -COX ₁₀ , -COX ₁₀ or -CONHX ₁₀ ;

X ₁₀ represents a hydrocarbyl group, a substituted hydrocarbyl group or a heterocyclo group;

Ac represents an acetyl group; or

R 1, R 1 and R ₁₀ independently have an alpha or beta stereochemical configuration.

In one embodiment, R ₂ represents ester (R _2a C (O) O-), carbamate (R _2a R _2b NC (O) O-), carbonate (R _2a OC (O) O-) or thiocarbamate (R _2a SC (O) O-), wherein R _1a and R _2b independently represent hydrogen, a hydrocarbyl group, a substituted hydrocarbyl group or a heterocyclo group. In a preferred embodiment, R ₂ represents an ester (R _2a C (O) O-), where R _2a represents an aryl group or a heteroaromatic group. In another preferred embodiment, R ₂ represents an ester (R, _a C (O) O-), wherein R 2 represents a substituted or unsubstituted phenyl group, a furyl group, a thienyl or a pyridyl group. In a highly preferred embodiment, R ₂ represents a benzoyloxy group.

In one embodiment of the invention, R ₇ represents R _7a COO-, where R 4 represents (i) a substituted or unsubstituted C ₂ to C ₈ alkyl (straight, branched or cyclic) group such as ethyl, propyl, butyl, pentyl or hexyl group; (ii) a substituted or unsubstituted C ₂ to C ₈ alkenyl (straight, branched or cyclic) group such as ethenyl, propenyl, butenyl, pentenyl or hexenyl; (iii) a substituted or unsubstituted C ₂ to C _g alkynyl (straight or branched) group such as ethynyl, propynyl, butynyl, pentynyl or hexynyl; (iv) a substituted or unsubstituted phenyl group; or (ν) a substituted or unsubstituted heteroaromatic group such as a furyl group, a thienyl group or a pyridyl group. The substituents may be hydrocarbyl groups, or any substituent containing a heteroatom, referred to throughout the description as a substituted hydrocarbyl group. In a preferred embodiment of the invention, R _7a represents an ethyl group, a straight, branched or cyclic propyl group, a straight, branched or cyclic butyl group, a straight, branched or cyclic pentyl group, a straight, branched or cyclic hexyl group, a straight or branched propenyl group, isobutenyl, furyl or thienyl. In another embodiment, R _7a represents a substituted ethyl group, a substituted propyl group (straight, branched or cyclic), a substituted propenyl group (straight or branched), a substituted isobutynyl group, a substituted furyl or a substituted thienyl group, where the substituent (s) are / are selected from a heterocyclo group, alkoxy group, alkenoxy group, alkoxy group, aryloxy group, hydroxy group, protected hydroxy group, keto group, acyloxy group, nitro group, amino group, amido group, thiol group, ketal group, acetal group, ect p and ether moieties, but not phosphorous containing moieties.

While in one embodiment of the present invention R ₉ is a keto group, in another embodiment it may have an alpha or beta stereochemical configuration, preferably a beta stereochemical configuration, and may be, for example, an alpha or beta-hydroxy group or an alpha or betaacyloxy group. For example, when R ₉ represents an acyloxy group, it may be an ester (R _9a C (O) O-), carbamate (R ^ R ^ NQCtyO-), carbonate (R _9a OC (O) O) or thiocarbamate (R _9a SC (O) O-), wherein R _9a and R _9b represent, independently of one another, hydrogen, a hydrocarbyl group, a substituted hydrocarbyl group or a heterocyclo group. If R ₉ represents an ester (R _9a C (O) O-), R _9a represents a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaromatic group. More preferably, R ₉ is an ester (N-C (O) O-), where R _9a represents a substituted or unsubstituted phenyl group, a substituted or unsubstituted furyl group, a substituted or unsubstituted thienyl group, or a substituted or unsubstituted pyridyl group. In one embodiment, R _g represents (R _9a C (O) O-), where R _9a represents a methyl group, ethyl group, propyl group (straight, branched or cyclic), butyl group (straight, branched or cyclic), pentyl group ( straight, branched or cyclic) or hexyl group. In another embodiment, R ₉ represents (R _9a C (O) O-), where Rg _a represents a substituted methyl group, a substituted ethyl group, a substituted propyl group (straight, branched or cyclic), substituted butyl group (straight, branched or cyclic) , a substituted pentyl group (straight, branched or cyclic) or a substituted hexyl group (straight, branched or cyclic), wherein the substituent (s) is / are selected from a heterocyclo group, alkoxy group, alkenyloxy group, alkyloxy group, aryloxy group, hydroxy group, a protected hydroxy group, a keto group, tsiloksi, nitro, amino, amido, thiol, ketal, acetal, ester and ether moieties, but not phosphorous containing moieties.

Exemplary X ₃ substituents include a substituted or unsubstituted C ₂ to C ₈ alkyl group, a substituted or unsubstituted C ₂ to C ₈ alkenyl group, a substituted or unsubstituted C ₂ to C ₈ alkynyl group, substituted or unsubstituted 5- or 6-atom heteroaromatic groups rings and a substituted or unsubstituted phenyl group. Preferred exemplary X ₃ substituents include substituted or unsubstituted ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclohexyl, isobutenyl, furyl, thienyl or pyridyl.

Exemplary X ₅ substituents include -COX ₁₀ , -COOX ₁₀ or -CONHX ₁₀ , where X ₁₀ represents a substituted or unsubstituted alkyl group, alkenyl group, phenyl or heteroaromatic group. Preferred exemplary X ₅ substituents include -COX ₁₀ , -COOOX ₁₀ or -CONHX ₁₀ , where X ₁₀ represents (i) a substituted or unsubstituted C ₍ to C ₈ alkyl group such as a substituted or unsubstituted methyl group, ethyl group, propyl group (straight, branched or cyclic), butyl group (straight, branched or cyclic), pentyl group (straight, branched or cyclic) or hexyl group (straight, branched or cyclic) (I) substituted or unsubstituted C ₂ to C ₈ alkenyl group as substituted or an unsubstituted ethenyl group, a propenyl group (straight, div Lone or cyclic), butenyl (straight, branched or cyclic), pentenyl (straight, branched or cyclic) or hexenyl (straight, branched or cyclic); (iii) substituted or unsubstituted C ₂ to C ₈ alkynyl such as substituted or an unsubstituted ethynyl group, a propynyl group (straight, branched or cyclic), a butynyl group (straight, branched or cyclic), a pentynyl group (straight, branched or cyclic) or hexinyl group (straight, branched or cyclic); (iv) a substituted or unsubstituted phenyl group or (v) a substituted or unsubstituted heteroaromatic group such as a furyl group, thienyl or pyridyl group, wherein the substituent (s) is / are selected from a heterocyclo group, alkoxy group, alkenyloxy group, alkoxy group, aryloxy group, hydroxy group, protected hydroxy group, keto group, acyloxy group, nitro group, amino group, amido group, thiol group, ketal group, acetal group, ester and ether moieties but not containing phosphorus moieties.

In a preferred embodiment, the taxanes of the present invention have the following structural formula (2):

where

R 1 represents R _7a COO-;

R ₁₀ represents a hydroxy group;

X ₃ represents a substituted or unsubstituted alkyl group, alkenyl group, alkynyl group or heterocyclo group;

X _{5 is} -COX ₁₀ , -COXX ₁₀ or -CONHX ₁₀ ;

X ₁₀ represents a hydrocarbyl group, a substituted hydrocarbyl group or a heterocyclo group;

R _7a represents a hydrocarbyl group, a substituted hydrocarbyl group or a heterocyclo group, wherein said hydrocarbyl or substituted hydrocarbyl group contains carbon atoms at the alpha and beta positions relative to the carbon atom linking the substituent R _7a ;

Bz represents a benzoyl group; and

Ac represents an acetal group.

For example, in this preferred embodiment, in which the taxane has structural formula (2), R _7a may be substituted or unsubstituted ethyl group, propyl or butyl group, preferably, substituted or unsubstituted ethyl or propyl group, more preferably, substituted or unsubstituted ethyl a group, and more preferably an unsubstituted ethyl group. While R _1a is selected from the above, in one embodiment X ₃ is selected from a substituted or unsubstituted alkyl group, an alkenyl group, a phenyl or heterocyclo group, a more preferably substituted or unsubstituted alkenyl group, a phenyl or heterocyclo group, more preferably substituted or an unsubstituted phenyl or heterocyclo group, and more preferably a heterocyclo group such as a furyl group, a thienyl or pyridyl group. While and X ₃ are selected from among these, in one embodiment X ₅ is selected from-COX ₁₀ wherein _{X] o} is phenyl, alkyl or heterocyclo, and still more preferably a phenyl group. Alternatively, while R _7a and X ₃ are selected from the above, in one embodiment X ₃ is selected from —COX ₁₀ , where X ₁₀ represents a phenyl group, an alkyl or heterocyclo group, more preferably a phenyl group, or X ₅ represents— COOX ₁₀ , where X ₁₀ represents an alkyl group, preferably a tertiary butyl group. Among the more preferred variants are taxanes of structural formula 2 wherein (i) X _s represents -COX ₁₀ , where X ₁₀ represents a tertiary butyl group, or X ₃ represents -COX ₁₀ , where X ₁₀ represents a phenyl group, (j) X ₃ represents a substituted or unsubstituted cycloalkyl group, alkenyl group, phenyl or heterocyclo group, more preferably, substituted or unsubstituted isobutenyl group, phenyl group, furyl group, thienyl or pyridyl group, more preferably, unsubstituted isobutenyl group, furyl group, a thienyl or pyridyl group; and (iii) R _{? a} represents an unsubstituted ethyl or propyl group, preferably an ethyl group.

Among the preferred variants are taxanes of structural formula (1) or (2), wherein R _? represents R _7a COO-, wherein _{R? a} represents an ethyl group. In this embodiment, X ₃ is preferably a cycloalkyl group, isobutenyl group, phenyl group, a substituted phenyl group such as a p-nitrophenyl group or a heterocyclo group, more preferably, a heterocyclo group, more preferably a furyl group, thienyl or pyridyl group; and X ₅ is preferably a benzoyl group, an alkoxycarbonyl or heterocyclocarbonyl group, and more preferably, a benzoyl group, a tertiary butoxycarbonyl or a tertiary amyloxycarbonyl group. As an alternative to this option; X ₃ represents a heterocyclo group; X ₅ represents a benzoyl group, an alkoxycarbonyl or heterocyclocarbonyl group, more preferably a benzoyl group, a tertiary butoxycarbonyl or a tertiary amyloxycarbonyl group, more preferably, a tertiary butoxycarbonyl group; R 1 represents a benzoyl group; R ₉ represents a keto group and a R ₁₄ hydrido group. As another alternative to this embodiment, X ₃ is a heterocyclo group; X ₃ represents a benzoyl group, an alkoxycarbonyl or heterocyclic carbonyl group, more preferably, a benzoyl group, a tertiary butoxycarbonyl or a tertiary amyloxycarbonyl group, more preferably, a tertiary butoxycarbonyl group; R 1 represents a benzoyl group; R 1 represents a keto group and an R ₁₄ hydrido group. As another alternative to this embodiment, X ₃ is a heterocyclo group; X ₃ represents a benzoyl group, an alkoxycarbonyl or heterocyclic carbonyl group, more preferably, a benzoyl group, a tertiary butoxycarbonyl or a tertiary amyloxycarbonyl group, more preferably, a tertiary butoxycarbonyl group; R ₂ represents a benzoyl group; R ₉ represents a keto group and R _{14 is a} hydroxy group. As another alternative to this embodiment, X ₃ is a heterocyclo group; X ₃ represents a benzoyl group, an alkoxycarbonyl or heterocyclic carbonyl group, more preferably, a benzoyl group, a tertiary butoxycarbonyl or a tertiary amyloxycarbonyl group, more preferably, a tertiary butoxycarbonyl group; R1 represents a benzoyl group; R 1 represents a hydroxy group and R _{14 a} hydroxy group. As another alternative to this embodiment, X ₃ is a heterocyclo group; X ₅ represents a benzoyl group, an alkoxycarbonyl or heterocyclic carbonyl group, more preferably, a benzoyl group, a tertiary butoxycarbonyl or a tertiary amyloxycarbonyl group, more preferably, a tertiary butoxycarbonyl group; R ₂ represents a benzoyl group; R 1 represents a hydroxy group and R _{14 a} hydrido group. As another alternative to this embodiment, X ₃ is a heterocyclo group; X ₃ represents a benzoyl group, an alkoxycarbonyl or heterocyclic carbonyl group, more preferably, a benzoyl group, a tertiary butoxycarbonyl or a tertiary amyloxycarbonyl group, more preferably, a tertiary butoxycarbonyl group; R ₂ represents a benzoyl group; R ₉ represents an acyloxy group and R _{14 a} hydroxy group. As another alternative to this embodiment, X ₃ is a heterocyclo group; X ₅ represents a benzoyl group, an alkoxycarbonyl or heterocyclocarbonyl group, more preferably a benzoyl group, a tertiary butoxycarbonyl or a tertiary amyloxycarbonyl group, more preferably, a tertiary butoxycarbonyl group; R ₂ represents a benzoyl group; R ₉ represents 10 acyloxy group and R ₁₄ hydrido group. In each of the alternatives to this option; when the taxane has structural formula (1), each of R _? and R ₁₀ may have a beta stereochemical configuration, any of Ry and R ₁₀ may have an alpha stereochemical configuration, R ₇ may have an alpha stereochemical configuration, while R _{I0 may} have a beta stereochemical configuration or R ₇ may have a beta stereochemical configuration configuration, and R ₁₀ may have an alpha sterochemical configuration. 20

Also preferred are taxanes of structural formula (1) or (2), wherein Ry represents R ^ COO-, where R _7a represents a propyl group. In this embodiment, X ₃ is preferably a cycloalkyl group, a 25 isobutenyl group, a phenyl group, a substituted phenyl group such as a p-nitro-phenyl group or a heterocyclo group, more preferably a heterocyclo group, more preferably a furyl group, thienyl or pyridyl group ; and X ₅ represents, 30 preferably, a benzoyl group, an alkoxycarbonyl or heterocyclic carbonyl group, and more preferably, a benzoyl group, a tertiary butoxycarbonyl or a tertiary amyloxycarbonyl group. As an alternative to this variant, 3 5 X ₃ represents a heterocyclo group; X ₅ represents a benzoyl group, an alkoxycarbonyl or heterocyclic carbonyl group, more preferably, a benzoyl group, a tertiary butoxycarbonyl or a tertiary amyloxycarbonyl group, 40 more preferably, a tertiary butoxycarbonyl group; R1 represents a benzoyl group; R ₉ represents a keto group and R _{14 a} hydrido group. As another alternative to this embodiment, X ₃ is a heterocyclo group; X ₅ represents a benzoyl 45 group, an alkoxycarbonyl or heterocyclic carbonyl group, more preferably, a benzoyl group, a tertiary butoxycarbonyl or a tertiary amyloxycarbonyl group, more preferably, a tertiary butoxycarbonyl group; R 50 is a benzoyl group; R 1 represents a keto group and an R ₁₄ hydrido group. As another alternative to this embodiment, X ₃ is a heterocyclo group; X ₅ represents a benzoyl group, an alkoxycarbonyl or heterocyclic carbonyl group, preferably a benzoyl group, a tert-butoxycarbonyl or a tertiary amyloxycarbonyl group, more preferably, a tert-butoxycarbonyl group; R 1 represents a benzoyl group; R ₉ represents a keto group and R _{14 is a} hydroxy group. As another alternative to this embodiment, X ₃ is a heterocyclo group; X ₅ represents a benzoyl group, an alkoxycarbonyl or heterocyclic carbonyl group, preferably a benzoyl group, a tert-butoxycarbonyl or a tertiary amyloxycarbonyl group, more preferably, a tert-butoxycarbonyl group; R1 represents a benzoyl group; R ₉ is hydroxy and R _J4 hydroxy group. As another alternative to this embodiment, X ₃ is a heterocyclo group; X ₅ represents a benzoyl group, an alkoxycarbonyl or heterocyclocarbonyl group, preferably a benzoyl group, a tertiary butoxycarbonyl or a tertiary amyloxycarbonyl group, more preferably a tertiary butoxycarbonyl group; R ₂ represents a benzoyl group; R ₉ represents a hydroxy group and R _{14 a} hydrido group. As another alternative to this embodiment, X ₃ is a heterocyclo group; X ₅ represents a benzoyl group, an alkoxycarbonyl or heterocyclic carbonyl group, more preferably, a benzoyl group, a tertiary butoxycarbonyl or a tertiary amyloxycarbonyl group, more preferably, a tertiary butoxycarbonyl group; R1 represents a benzoyl group; R ₉ represents an acyloxy group and R _{14 a} hydroxy group. As another alternative to this embodiment, X ₃ is a heterocyclo group; X ₅ represents a benzoyl group, an alkoxycarbonyl or heterocyclocarbonyl group, preferably a benzoyl group, a tertiary butoxycarbonyl or a tertiary amyloxycarbonyl group, more preferably a tertiary butoxycarbonyl group; R ₂ represents a benzoyl group; R 4 represents an acyloxy group and R _{14 a} hydrido group. In each of the alternatives to this variant, when the taxane has structural formula (1), each of R ₇ and R _{| 0} may have a beta stereochemical configuration, each of R _? and R ₁₀ may have an alpha stereochemical configuration, R 10 may have an alpha stereochemical configuration, while R _{10 may} have a beta stereochemical configuration, or R ₇ may have a beta stereochemical configuration, and R ₁₀ may have an alpha stereochemical configuration.

Taxanes of general formula I can be prepared by treating beta-lactam with a taxane tetracyclic alkoxide core and with C-13 metal oxide substituents to give compounds with C-13 beta-amido ester substituent (as described in more detail in Holton US Patent 5,466,834), after which the protecting hydroxy groups are removed, Betalactam has the following structural formula (3):

(3) where P ₂ represents a protecting hydroxy group and X ₃ and X ₅ have the meaning defined above and the oxoxide has the structural formula (4):

where M represents a metal or ammonia residue, P ₁₀ represents a hydroxy protecting group and R ₂ , R 1, R 1 and R ₁₄ have the meanings defined above.

Alkoxide 4 can be prepared from 10deacetylbaccatin III (or a derivative thereof) by selectively protecting the C-10 hydroxyl group and then treated with a metal amide. In one embodiment of the present invention, the C-10 hydroxyl group of 10-deacetylbaccatin III is selectively protected with a silyl group using, for example, silylamide or bisilylamide as a silylating agent. Preferred silylating agents include three (hydrocarbyl) silyltrifluoromethylacetamides, and bis three (hydrocarbyl) moieties represent substituted or unsubstituted alkyl or aryl groups) such as N, O-L13- (trimethylsilyl) trifluoroacetamide, N, 0bis-3-triethylamide, triethylamino) -N-triethylsilyltrifluoroacetamide hN, O-bis- (t-butyl-dimethylsilyl) trifluoroacetamide. The silylating agents may be used individually or in combination with a catalytic amount of base as alkali metal base. Alkali metal amides, in general, as lithium amide catalysts such as, in particular, is preferably lithium hexamethyldisilazide. The solvent for the selective silencing reaction is preferably an ether solvent such as tetrahydrofuran. Alternatively, other solvents such as ether or dimethoxyethane may be used. The temperature at which C (10) is performed is selective silencing not very critical. Generally, it is carried out at 0 ° C or higher.

The selective esterification of the C (7) hydroxyl group of the C (10) protected taxane can be carried out using any of a variety of acylating agents, including substituted or unsubstituted carboxylic acid derivatives, for example, carboxylic acid halides, anhydrides, dicarbonates, isocyanates and haloformats, the examples of which are not exhausted. For example, the C (7) hydroxyl group of 10protected-10-deacetylbaccatin III may be selectively acylated with dibenzyl dicarbonate, diallyldicarbonate, 2,2,2-trichloroethyl chloroformate, benzyl chloroformate or other ordinary acylating agent. The acylation of the C (7) hydroxyl group of the C (10) protected taxane is more efficient and more selective than the acylation of the C (7) position of 7,10-dihydroxytaxane as 10-DAB; or in other words, after the C (10) hydroxyl group is protected, a significant difference in the reactivity of the other C (7), C (13) and C (1) hydroxyl groups is observed. These acylation reactions may optionally be carried out in the presence or absence of an amine base.

Derivatives of 10-deacetylbaccatin III with alternative substituents of C (2), C (9) and C (14) and methods for their preparation are known in the art. Taxane derivatives with acyloxy substituents other than the benzyloxy group of C (2) can be prepared, for example, as described in Holton et al., U.S. Pat. No. 5,728,725 or Kingston et al., U. S. Pat. No. 6,002,023. Taxes with acyloxy or hydroxy substituents of the C (9) in place of the keto group can be prepared, for example, 5 as described in Holton et al., U.S. Pat.

No. 6,011,056 or Gunawardana et al., U. S. Pat. No. 5,352,806. Taxes with the beta hydroxy substituent of C (14) can be obtained from natural 14hydroxy-10-deacetylbaccatin III. 10

Methods for preparing and dissolving the beta-lactam starting material are generally well known. For example, beta-lactam can be prepared as described in Holton et al., U.S. Pat. No. 5,430,160, and the resulting enantiomeric mixtures of beta-lactams can be dissolved by stereoselective hydrolysis using a lipase or enzyme, as described, for example, in Patel, U.S. Pat. No. 5,879,929, Patel, U. S. Pat. No. 5,567,614, or use hepatic homogenase; as described, for example, in PCT Patent Application No. 00/41204. In a preferred embodiment, in which the beta-lactam is a furyl substituent at the C (4) position, the beta-lactam can be prepared as shown in the following reaction scheme:

Step D

CAN. CH ₃ CN

Step F

Step F

(-) 10

p-TsOH ^ ΟΜβ

(-) 12 (+) 11 where Ac represents the acetyl group, 40 NEt ₃ represents triethylamine, CAN represents cerium ammonium nitrate and p-TsOH represents ptoluenesulfonic acid. The absorption from bovine liver can be accomplished, for example, by combining an enantiomeric mixture of beta-lactam with a suspension of bovine liver (obtained, for example, by adding 20 g of frozen liver in a blender, and then adding a buffer solution with pH 8 to give a final volume 11).

Compounds of formula 1 of the present invention are useful for inhibiting tumor growth in mammals, including humans, and it is advisable to take them in the form of a pharmaceutical composition comprising an effective amount of an antitumor compound of the present invention in combination with at least one pharmaceutical or pharmacological carrier. The carrier known in the art, further, as an excipient, excipient, adjuvant, adjuvant or diluent, may be any substance that is pharmaceutically inert, provides a suitable consistency or form of the composition and does not reduce the therapeutic effect of the antitumor compounds. A carrier is defined as "pharmaceutically or pharmacologically acceptable" if it does not cause an undesirable, allergic or other adverse reaction when administered to mammals, including humans.

Pharmaceutical compositions containing the antitumor compounds of the present invention can be prepared by the conventional method. The appropriate formula depends on the route of administration selected. The compositions of the present invention may be prepared for each route of administration such that the target tissue is accessible during this time. Suitable routes of administration include, but are not limited to, oral, parenteral (e.g., intravenous, intra-arterial, subcutaneous, rectal, intramuscular, intra-orbital, intracapsular, intraspinal, intraperitoneal, or intracranial, intraperitoneal, intrasternal, intraspera, transperitoneal, intraperitoneal, intranasal, intrasternal, or intrasternal) ), intravesical, intrathecal, enteral, pulmonary, intralymphatic, intracavital, vaginal, transurethral, intradermal, ingestion through the ears, through the mammary glands, through the mucous membranes, buccal, orthotopic, intratracheal, percutaneous, endoscopic, transmucosal, sublingual and intestinal administration.

The pharmaceutically acceptable carriers used in the compositions of the present invention are well known to those skilled in the art and their selection is based on a number of factors: the particular antitumor compound used and its concentration, stability and necessary accessibility to the body; the disease, malaise or condition being treated with the composition; the object, its age, size and general condition; as well as the route of reception. Suitable carriers are readily determined by one of ordinary skill in the art (see, e.g., J. G. Naim, in Remington's Pharmaceutical Science (A. Gennaro, ed), Mack Publishing Co., Easton, Pa., (1985), pp. 1492-1517, contents which is included here for reference).

Preferably, the compositions are formulated as tablets, dispersible powders, pills, gelatin capsules, caplets, gels, liposomes, granules, solutions, suspensions, emulsions, syrups, elixirs, tablets, dragees, candies or any other dosage that may be used. taken orally. The techniques and compositions for oral dosage preparation that can be used in the present invention are described in the following references: 7 Modem Pharmaceutics, Chapters 9 and 10 (Banker & Rhodes, Editors, 1979); Liaberman et al., Pharmaceutical Dosage Forms: Tablets (1981); and Ansel, Introduction to Pharmaceutical Dosage Forms 2nd Edition (1976).

The compositions of the present invention for oral administration include an effective amount of an antitumor compound of the present invention in a pharmaceutically acceptable carrier. Suitable carriers for solid dosage include sugars, starches and other conventional substances, including lactose, talc, sucrose, gelatin, carboxymethylcellulose, agar, mannitol, sorbitol, calcium phosphate, calcium carbonate, sodium carbonate, kaolin, alginic acid, algaine starch, potato starch, saccharin sodium, magnesium carbonate; tragacanth, microcrystalline cellulose, colloidal silica, sodium modified carmellose, magnesium stearate and stearic acid. In addition, such solid dosages may or may not be coated by known techniques; for example, to delay disintegration and absorption.

Also, the antitumor compounds of the present invention may preferably be prepared for parenteral administration, for example, prepared for injection, given intravenously, intraarterially, subcutaneously, rectally, intramuscularly, intra-orbital, intracapsular, intraspinal, intraperitoneally or intraperitoneally. The compositions of the invention for parenteral administration include an effective amount of an antitumor compound of the present invention in a pharmaceutically acceptable carrier. Dosages suitable for parenteral administration include solutions, suspensions, dispersions, emulsions or any other dosage that can be administered parenterally. Techniques and compositions for the preparation of parenteral dosages are known to those skilled in the art.

Suitable carriers used in the preparation of liquid dosages for oral or parenteral administration include non-aqueous, pharmaceutically acceptable polar solvents such as oils, alcohols, amides, esters, ethers, ketones, hydrocarbons and their corresponding mixtures, as well as 5 and water, saline solutions , dextrose solutions (eg, DW5), electrolyte solutions or any other aqueous, pharmaceutically acceptable liquid.

Suitable non-aqueous, pharmaceutically acceptable 10 polar solvents include, but are not limited to, the following alcohols: alcohols (e.g., alpha-glycerolformal, betaglycerolformal, 1,3-butylene glycol, aliphatic or aromatic alcohols having 2-30 carbon atoms such as 15 methanol, ethanol, propanol, isopropanol, butanol, tertiary butanol, hexanol, oxanol, amylenhydrate benzyl alcohol, glycerol (glycerol), glycol, hexylene glycol, tetrahydrofurfuryl alcohol, lauryl alcohol, ethyl ester or alkyloalkyl esteryl acetyl of fatty alcohols such as polyalkylene glycols (e.g. polypropylene glycol, polyethylene glycol), sorbitan, sucrose and cholesterol); amides (e.g., dimethylacetamide (DMA), benzylbenzoate DMA, 25 dimethylformamide, L1- (beta-hydroxyethyl) lactamide, N, N-dimethylacetamide amides, 2pyrrolidinone, 1-methyl-2-pyrrolidinone or polyvinylpyrrolidone); esters (e.g., 1-methyl2-pyrrolidinone, 2-pyrrolidinone, acetate esters 30 such as monoacetin, diacetin and triacetin, aliphatic or aromatic esters such as ethyl caprylate or octanoate, alkyl oleate, benzylbenzoate, benzyl acetate, dimethylsulfonate) , di- or triglycyl citrates or 35 tartrates, ethylbenzoate, ethyl acetate, ethyl carbonate, ethyl lactate, ethyl oleate, fatty acid and sorbitan esters, fatty acid esters and derivatives of PEG, glyceryl monostearate; fatty 40 acids such izopropilmiristrat, esters of fatty acids and derivatives of PEG as PEGhidroksioleat and PEG-hydroxystearate, N-methyl pyrrolidinone, pluronic 60, polyesters of oleic acid and polyoxyethylene 45 as poly (ethoxylated) _{3 (Kb0} sorbitolpoli (oleate) _2l, poly ( _{oxyethylene)] 5 20} monoricinoleate, polyoxyethylene sorbitan esters such as polyoxyethylenesorbitan monooleate, polyoxyethylenesorbitan monopalmitate, polioksietilensorbitanmonolaurag, 50 polioksietilensorbitanmonostearat and Polysorbate® 20, 40, 60 or 80 from ICI Americas, Wilmington, DE, polyvinylpyrrolidone Lidon, modified alkyloxy fatty acid esters such as hydrogenated with polyoxyl 40 castor oil and polyoxyethylated castor oil (eg, Cremophorr EL solution or Cremophor® RH 40 solution), saccharide fatty acid esters (eg, condensation product of monosaccharide, e.g. pentoses such as ribose, ribulose, arabinose, xylose, lyxose and xylulose, hexoses such as glucose, fructose, galactose, mannose and sorbose, trioses, tetroses, heptoses and octoses), disaccharides (e.g. sucrose, maltose or lactose, or lactose ehni mixtures thereof with C ₄ C ₂₂ fatty acid / s (for example, saturated fatty acids such as caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid and stearic acid, and unsaturated fatty acids such as palmitoleic acid, oleic acid, elaidic acid , erucic acid and linoleic acid) or steroidal esters); alkyl, aryl or cyclic ethers having 2-30 carbon atoms (e.g. diethyl ether, tetrahydrofuran, dimethylisosorbide, diethylene glycol monoethyl ether); glycofurol (polyethylene glycol ether and tetrahydrofurfuryl alcohol); 3-30 carbon atom ketones (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone); aliphatic, cycloaliphatic or aromatic hydrocarbons having 4-30 carbon atoms (e.g., benzene, cyclohexane, dichloromethane, dioxolans, hexane, p-decane, p-dodecane, p-hexane, sulfolane, tetramethylsulfone, toluene, dimethylsulfonylmethylsulfonylmethylsulfonate) ); oils of mineral, vegetable, animal, natural or synthetic origin (for example, mineral oils such as aliphatic or wax-based hydrocarbons, aromatic hydrocarbons, mixed aliphatic and aromatic hydrocarbons and refined paraffin oil, vegetable oils such as flaxseed oil, vegetable oils such as flaxseed oil saffron, soy, castor oil, cottonseed oil, peanut oil, rapeseed oil, coconut oil, palm oil, olive oil, corn oil, corn germ oil, sesame oil, peanut oil, glycerides such as mono-, di - or triglycerides, animal oils such as fish oil, cetaceum, spermacet, cod liver oil, haliver, squalane and shark liver oil, oleic oils and polyoxyethylated castor oil); alkyl or aryl halides having 1-30 carbon atoms and optionally more than one halogen substituent; methylene chloride; monoethanolamine; petroleum ether; trolamine; omega-3 polyunsaturated fatty acids (eg, alpha-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid or docosahexaenoic acid); 12-hydroxystearic acid polyglycol ester and polyethylene glycol (Solutol® HS-15 from BASF, Ludwigshafen, Germany); polyoxyethylene glycerol; sodium laurate; sodium oleate or sorbitan monooleate.

Other pharmaceutically acceptable solvents that may be used in the present invention are well known to those skilled in the art and are described in The Chemotherapy Source Book (Williams & Wilkens Publishing), The Handbook of Pharmaceutical Excipients, (American Pharmaceutical Association, Washington, D C, and The Pharmaceutical Society of Great Britain, London, England, 1968), Modem Pharmaceutics, (G. Banker et al., Eds., 3d ed.) (Marcel Dekker, Inc., New York, New York, 1995 ), The Pharmacological Basis of Therapeutics, (Goodman & Gilman, McGraw Hill Publishing), Pharmaceutical Dosage Forms, (H. Lieberman et al., Eds.), (Marcel Dekker, Inc., New York, New York, 1980). Remington's Pharmaceutical Science (A. Gennaro, ed., 19th ed.) (Mack Publishing, Easton, PA, 1995). The United States Pharmacopeia 24, The National Formulary 19, (National Publishing, Philadelphia, PA, 2000), A. J. Spiegel et al., And Use of Nonaqueous Solvents in Parenteral Products, Journal of Pharmaceutical Science, Vol. 52, no. 10, pp. 917-927 (1963).

Preferred solvents include those that stabilize the antitumor compounds, such as oils rich in triglycerides, for example, saffron oil, soybean oil or mixtures thereof, and modified alkyloxy fatty acid esters such as hydrogenated with polyoxyl 40 castor oil and polyoxyethylene (for example, Cremophor® EL solution or Cremophor® RH40 solution). Triglycerides that are commercially available include Intralipid Emulsified Soybean Oil (KabiPharmacia Inc., Stockholm, Sweden), Nutralipid Emulsion (McGaw, Irvine, California), Liposyn® II

20% emulsion (20% fat emulsion solution containing 100 mg saffron oil, 100 mg soybean oil, 12 mg egg phosphatides and 25 mg glycerol per ml solution; Abbott Laboratories, Chicago, Illinois), Liposyn® III 2% emulsion ( 2% fat emulsion solution containing 100 mg saffron oil, 100 mg soybean oil, 12 mg egg phosphatides and 25 mg glycerol per ml solution; Abbott Laboratories, Chicago, Illinois), natural or synthetic glycerol derivatives containing the docosahexaenoyl group of levels between 25% and 100% by weight of total fatty acid content (Dhasco® (from Martek Biosciences Corp., Columbia, MD) DHA Maguro® (from Daito Enterprises, Los Angeles, CA ), Soyacai® and Travemulsion® Ethanol is the preferred solvent for dissolving the antitumor compound to obtain solutions, emulsions and the like.

For the purposes of the compositions of the present invention, additional secondary solvents well known in the pharmaceutical industry may be incorporated for various purposes. These components, for the most part, give the composition characteristics that enhance the retention of the antitumor compound at the site of administration, protect the stability of the composition, control pH, facilitate the processing of the antitumor compound in pharmaceutical formulations and the like. Preferably, each of these components is individually represented by less than 15% by weight of the total composition, preferably by less than 5% by weight, and even more preferably, by less than 0.5% by weight of the total composition. Some components, such as filters and solvents, can reach up to 90% by weight of the total composition, as is well known in the art. Such additives include cryoprotectants for the prevention of the taxation of taxane, surfactants, moisturizing or emulsifying agents (eg, lecithin, polysorbate-80, Tween® 80, pluronic 60, polyoxyethylene stearate), preservatives (eg ethyl p-hydroxybenzoxybenzoxybenzo) (e.g., benzyl alcohol, phenol, m-cresol, chlorobutanol, sorbic acid, thimerosal, and paraben), pH-correcting or buffering agents (e.g., acids, bases, sodium acetate, sorbitan monolaurate), agents, eg, osmotic corrections (e.g. erin), thickeners (for example, aluminum monostearate, stearic acid, cetyl alcohol, stearyl alcohol, gum arabic, methylcellulose, hydroxypropylcellulose, tristearin, cetyl wax esters, polyethylene glycol), colorants, silicones, silicones, silicones, silicones, ), adhesives (for example, bentonites), surfactants, blowing agents, flavorings, sweeteners, adsorbents, fillers (eg sugars such as lactose, sucrose, mannitol or sorbitol, cellulose or calcium phosphate), diluent (e.g., water, brine, electrolyte solutions), carriers (e.g., starches such as corn starch, wheat starch, rice starch or potato starch, gelatin, tragacanth, methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, polycarbonylcellulose, polymers, cellulose) , disintegrants (e.g., starches such as corn starch, wheat starch, rice starch, potato starch or carboxymethyl starch, spatially cross-linked polyvinylpyrrolidone, agar, alginic acid or its corresponding l as sodium alginate, modified sodium cellulose or crospovidone), lubricants (e.g., silicon, talc, stearic acid or its corresponding salts such as magnesium stearate or polyethylene glycol), enveloping agents (e.g., concentrated sugar solutions including gum arabic, talipolin, talipid carbopol gel, polyethylene glycol or titanium dioxide) and antioxidants (e.g. sodium metabisulfite, sodium bisulfite, dextrose, phenols and thiophenols), In a preferred embodiment, the pharmaceutical composition of the present invention includes at least one non-aqueous, pharmaceutically acceptable solvent and an antitumor compound with ethanol solubility of at least about 100, 200, 300, 400,500,600,700 or 800 mg / ml are present. Without being bound by a specific theory, it is believed that the solubility of the antitumor compound in ethanol is directly related to its effectiveness. The antitumor compound can also be crystallized from solution. In other words, a crystalline antitumor compound, such as compound 1393, can be dissolved in a solvent to form a solution, and then recrystallized by evaporating the solvent without forming an amorphous antitumor compound. It is also advisable that the antitumor compound has an ID50 value (e.g., a drug concentration conferring 50% inhibition of colony formation) at least 4, 5,6,7,8,9, or 10 times that of paclitaxel when measured against the protocol annexed to the working examples.

The dosage of administration by these routes may be interrupted or continuous depending on, for example, the physiological condition of the patient, whether the purpose of administration is therapeutic or prophylactic, as well as other factors known to those skilled in the art.

Standard specialists in the field of cancer treatment can readily determine the dosage and dosage regimen of the pharmaceutical composition of the present invention. It is understandable that the dosage of the anticancer compounds will depend on the age, sex, general health and weight of the patient, the type of additional treatment, if any, the frequency of treatment and the nature of the desired effect. For each treatment model, the specific amount of antitumor substance received, as well as the dosage regimen required to achieve the beneficial effects described herein, will also depend, in part, on a number of factors such as the bioavailability of the antitumor compound, the disease being treated, the desired therapeutic dose, and other factors apparent to those skilled in the art. The dosage administered to animals, and especially to humans, in the context of the present invention should be sufficient to elicit the desired therapeutic response in the animal for an acceptable period of time. Preferably, an effective amount of the antitumor compound, whether taken orally or otherwise, is considered to be any amount that is capable of eliciting the desired therapeutic response when taken appropriately. It is recommended that the compositions for oral administration be prepared such that a single dose in one or more oral formulations a contains at least 20 mg of the antitumor compound per ml. patient surface or at least 50, 100, 150, 200, 300, 400 or 500 mg of the antitumor compound per m ² patient surface having an average human body surface area of 1.8 µL It is preferable that a single dose of the oral composition is containing from about 20 to about 600 mg of the antitumor compound per patient surface, preferably from about 25 to about 400 mg / m 2, more preferably from about 40 to about 300 mg / m 2, and most preferably from about 50 to about 200 mg / nA Preferably, the compositions for parenteral administration are formulated in such a way that is a single dose in one or more oral formulations containing at least 20 mg of the antitumor compound per m ² patient surface or at least 40, 50, 100, 150, 200, 300, 400 or 500 mg of the antitumor compound per m ² patient surface . Preferably, a single dose in one or more parenteral formulations contains from about 20 to about 500 mg of the antitumor compound per m 2 of the patient's surface, preferably from about 40 to about 400 mg / m 2, and more preferably from about 60 to about 350 mg / nA The dosage may vary depending on the dosage schedule, which can be adjusted as necessary to achieve the desired therapeutic effect. It should be noted that the effective dosage ranges indicated herein do not limit the invention and represent preferred dosage ranges. It is understandable and perfectly possible for standard practitioners in the art to determine the most appropriate dosage for the particular case without the need for extreme experiments.

The recommended concentration of the antitumor compound in a liquid pharmaceutical composition is from about 0.01 mg to about 10 mg per ml of the composition, a more preferred concentration is from about 0.1 mg to about 7 mg per ml, more preferably a concentration from about 0.5 mg to about 5 mg per ml, most preferably from about 1.5 mg to about 4 mg per ml. Relatively low concentrations are preferred because the antitumor compound is more soluble in solution at low concentrations. The concentration of the antitumor compound in a solid pharmaceutical composition for oral administration is preferably between about 5 wt% and 50 wt% relative to the total weight of the composition, more preferably between about 8 wt% and about 40 wt%, and most preferably is between about 10% by weight and about 30% by weight.

In one embodiment, oral administration solutions are prepared by dissolving the antitumor compound in any pharmaceutically acceptable solvent that can dissolve the compound (e.g., ethanol or methylene chloride) to form a solution. A suitable volume of carrier is also added to the solution, also in the form of a solution, for example, as a solution of Cremophor® EL, stirring to obtain a pharmaceutically acceptable solution for oral administration to a patient. Optionally, such solutions may or may not contain minimal amounts of ethanol, which is known to be taken at certain concentrations in oral compositions to cause adverse physiological effects.

In another embodiment, powders or tablets are prepared for oral administration by dissolving an antitumor compound in any pharmaceutically acceptable solvent that can dissolve the compound (e.g., ethanol or methylene chloride) to form a solution. Optionally, the solvent may be evaporated by drying the solution in vacuo. Before drying, an additional carrier such as Cremophor® EL solution may be added to the solution. The resulting solution was dried in vacuo to give a glass mass. The glass mass is then mixed with the carrier to form a powder. The powder may be mixed with excipients or other conventional tablet agents and processed for the preparation of a tablet for oral administration by a patient. In addition, the powder may be added to any liquid carrier as described above to form a solution, emulsion, suspension or other oral preparation.

Emulsions for parenteral administration may be prepared by dissolving an antitumor compound in any pharmaceutically acceptable solvent that can dissolve the compound (e.g., ethanol or methylene chloride) to form a solution. A suitable volume of carrier is also added to the solution, also in the form of an emulsion, for example, as an emulsion of Liposyn® II or Liposyn® III, stirring the preparation of a pharmaceutically acceptable emulsion for parenteral administration by a patient. Optionally, such emulsions may or may not contain minimal amounts of ethanol or a solution of Cremophor (R), which is known to be taken at certain concentrations in parenteral compositions to cause an adverse physiological effect.

Parenteral administration solutions can be prepared by dissolving an antitumor compound in any pharmaceutically acceptable solvent that can dissolve the compound (e.g., ethanol or methylene chloride) to form a solution. A suitable volume of carrier is also added to the solution, also in the form of a solution, for example, as a HaCremophorr solution, stirring to obtain a pharmaceutically acceptable solution for parenteral administration to a patient. Optionally, such solutions may or may not contain minimal amounts of ethanol or a solution of Cremophor (R), which is known to be taken at certain concentrations in parenteral compositions to cause an adverse physiological effect.

Optionally, the emulsions or oral or parenteral administration solutions described above may be packaged in IV plastic bags, vials or other conventional containers, in concentrated form or dissolved in any pharmaceutically acceptable liquid as saline, to obtain an acceptable concentration of taxane. prior to administration, as known in the art.

Definitions

The terms "hydrocarbon" and "hydrocarbyl group" as used herein describe organic compounds or radicals composed exclusively of carbon and hydrogen elements. These moieties include alkyl, alkenyl, alkynyl and aryl moieties. These moieties also include alkyl, alkenyl, alkynyl and aryl moieties substituted by other aliphatic or cyclic hydrocarbon groups such as alkaryl, alkenaryl and alkynaryl. Unless otherwise indicated, these moieties preferably include from 1 to 20 carbon atoms.

The "substituted hydrocarbyl" moieties described herein are hydrocarbyl moieties substituted by at least one non-carbon atom, including moieties in which the carbon chain is replaced by a heteroatom such as nitrogen, oxygen, silicon, phosphorus, boron, sulfur or halogen. These substituents include a halogen atom, a heterocyclo group, an alkoxy group, an alkoxy group, an alkoxy group, an aryloxy group, a hydroxy group, a protected hydroxy group, a keto group, an acyl group, an acyloxy group, a nitro group, an amino group, an amido group, a nitro group, cyano group, thiol group, ketals, acetals, esters and ethers.

The term "heteroatom" means atoms other than carbon and hydrogen.

The "substituted methyl" moieties described herein are methyl groups in which the carbon atom is covalently bonded to at least one heteroatom and optionally to hydrogen such as the heteroatom being, for example, nitrogen, oxygen, silicon, phosphorous, boron, sulfur or halogen atom. In turn, the heteroatom can be substituted by other atoms to give a heterocyclo group, alkoxy group, alkeny group, alkyloxy group, aryloxy group, hydroxy group, protected hydroxy group, oxy group, acyloxy group, nitro group, amino group, amido a group, a thiol group, ketals, acetals, esters or ether moieties.

The "hetero substituted acetate" moieties described herein are acetate groups in which the carbon of the methyl group is covalently bonded to at least one heteroatom and optionally to hydrogen such as the heteroatom being, for example, nitrogen, oxygen, silicon, phosphorus, boron, sulfur or a halogen atom. In turn, the heteroatom can be substituted by other atoms to give a heterocyclo group, alkoxy group, alkeny group, alkyloxy group, aryloxy group, hydroxy group, protected hydroxy group, oxy group, acyloxy group, nitro group, amino group, amido a group, a thiol group, ketals, acetals, esters or ether moieties.

Unless otherwise indicated, the alkyl groups described herein are preferably a lower alkyl group containing from one to eight carbon atoms in the main chain and up to 20 carbon atoms. They may be straight or branched or cyclic, comprising an ethenyl group, propenyl group, isopropenyl group, butenyl group, isobutenyl group, hexenyl group and the like.

Unless otherwise indicated, the alkynyl groups described herein are preferably a lower alkynyl group containing from two to eight carbon atoms in the main chain and up to 20 carbon atoms. They may be straight or branched, including an ethynyl group, a propynyl group, a butynyl group, an isobutynyl group,

652-9 hexynyl group and others.

The terms "aryl group" or "ar" used herein individually or as part of another group mean optionally substituted homocyclic, aromatic groups, preferably, monocyclic or bicyclic groups containing from 6 to 12 carbon atoms in the ring moiety, such as a phenyl group, a biphenyl group, a substituted phenyl group, a substituted biphenyl group, or a substituted naphthyl group. Among the more preferred aryl groups are the phenyl and substituted phenyl groups.

The terms "halogen atom" or "halo" used herein individually or as part of another group mean a chlorine, bromine, fluorine or iodine atom.

The terms "heterocyclic" or heterocyclic group "used herein individually or as part of another group means substituted, optionally, fully saturated or unsaturated, monocyclic or bicyclic, aromatic or non-aromatic groups with at least one heteroatom in at least one ring, preferably, with 5 or 6 atoms in each ring. Preferably, the heterocyclo group has 1 or 2 oxygen atoms, 1 or 2 sulfur atoms and / or 1 to 4 nitrogen atoms in the ring and may be bonded to the rest of the molecule by a carbon atom or heteroatom. Examples of a heterocyclo group include heteroaromatic furyl group, thienyl group, pyridyl group, oxazolyl group, pyrrolyl group, indolyl group, quinolyl or isoquinolyl group and the like. Examples of substituents include one or more of the following groups: hydrocarbyl group, substituted hydrocarbyl group, keto group, hydroxy group, protected hydroxy group, acyl group, acyloxy group, alkoxy group, alkeny group, alkyloxy group, aryloxy group, halogen atom, amido group, amino group, nitro group, cyano group, thiol group, ketals, acetals, esters and ethers.

The term "heteroaromatic group" used herein individually or as part of another group means substituted, optionally substituted, aromatic groups with at least one heteroatom in at least one ring, preferably with 5 or 6 atoms in each ring. Preferably, the heteroaromatic group has 1 or 2 oxygen atoms, 1 or 2 sulfur atoms and / or 1 to 4 nitrogen atoms in the ring and may be a carbon atom or a heteroatom. Examples of heteroaromatic groups include furyl group, thienyl group, pyridyl group, oxazolyl group, pyrrolyl group, indolyl group, quinolyl or isoquinolyl group and the like. Examples of substituents include one or more of the following groups: hydrocarbyl group, substituted hydrocarbyl group, keto group, hydroxy group, protected hydroxy group, acyl group, acyloxy group, alkoxy group, alkeny group, alkyloxy group, aryloxy group, halogen atom, amido group , amino group, nitro group, cyano group, thiol group, ketals, acetals, esters and ethers.

The term "acyl group" used herein individually or as part of another group means the moiety obtained by the removal of the hydroxyl group from the -COOH group of an organic carboxylic acid, for example, RC (O) -, where R represents R \ R ^ O -, R 1, R 2 N - or R 4 S - as R represents a hydrocarbyl group, a hetero substituted hydrocarbyl group or a heterocyclo group, and R 4 represents a hydrogen atom, a hydrocarbyl group or a substituted hydrocarbyl group.

The term "acyloxy", used herein individually or as part of another group, means an acyl group as described above, bonded through an oxygen bridge (-O-), for example, RC (O) O-, where R has the meaning defined in connection with the term "acyl group".

Unless otherwise indicated, the alkoxycarbonyloxy moieties described herein include a lower hydrocarbon or substituted hydrocarbon or substituted hydrocarbon moieties.

Unless otherwise indicated, the carbamoyloxy moieties described herein are carbamic acid derivatives in which one or both of the hydrogen atoms of the amino group are optionally substituted by a hydrocarbyl moiety, a substituted hydrocarbyl moiety or a heterocyclo moiety.

The terms "hydroxyl protecting group" and "hydroxy protecting group" as used herein mean a group that can protect a free hydroxyl group ("substituted hydroxyl") which, in accordance with the reaction requiring protection, can be removed without the rest of the molecule is affected. A large number of protecting groups for the hydroxyl group and their corresponding synthesis can be found in "Protective Groups in Organic Synthesis" by T. W. Greene, John Wiley and Sons, 1981, or Fieser & Fieser. Examples of hydroxyl protecting groups include methoxymethyl group, 1-ethoxyethyl group, benzyloxymethyl group, (.beta.trimethylsilylethoxy) methyl group, tetrahydropyranyl group, 2,2,2-trichloroethoxycarbonyl group Ebutyl (diphenyl) silyl group trialkylsilyloxy group trichloxylyloxycarbonyl , 2-trichloroethoxymethyl group.

As used herein, "Ac" means acetyl group "Bz" means benzoyl group; "Et" means an ethyl group; "Me" means methyl group "Ph" means phenyl group "Pr" means propyl group; "You" means a butyl group; "At" means an amyl group; "Srgo" means cyclopropyl group "iPr" means isopropyl group; "TBu" and "t-Bu" mean a tertiary butyl group; "R" means a lower alkyl group, unless otherwise indicated; "Py" means pyridine or pyridyl group "TES" means triethylsilyl group; "TMS" means trimethylsilyl group; "LAH" means lithium aluminum hydride; "10DAB" means 10-desacetylbaccatin III; "Amino protecting groups" include, but are not limited to, carbamates, for example, 2,2,2trichloroethylcarbamate or tertiary butyl carbamate; "Protected hydroxy group" means - OP, where P represents a hydroxy protecting group; "PhCO" means a phenylcarbonyl group; "TBuOCO" and "Boc" mean a tertiary butoxycarbonyl group; "TAmOCO" means a straight amyloxycarbonyl group; "2-FuCO" means a 2-furylcarbonyl group; "2-ThCO" means a 2-thienylcarbonyl group; "2-RuCO" means a 2-pyridylcarbonyl group; "3-RuCO" means a 3-pyridylcarbonyl group; "4-RuCO" means a 4-pyridylcarbonyl group; "C ₄ H ₇ CO" means a butenylcarbonyl group; "TC ₃ H ₅ CO" means a trans-propenylcarbonyl group; "EtOCO" means an ethoxycarbonyl group; "IbueCO" means an isobutylcarbonyl group; "IBuCO" means an isobutylcarbonyl group; "IBuOCO" means an isobutoxycarbonyl group; "IPrOCO" means an isopropyloxycarbonyl group; Means a n-propyloxycarbonyl group; Means a n-propylcarbonyl group; "Ibue" means an isobutenyl group; "THF" means tetrahydrofuran; "DMAP" means 4-dimethylaminopyridine; "LHMDS" means lithium hexamethyldisilazanide.

An exemplary embodiment of the invention

10-triethylsilyl-10-deacetylbaccatin III

To a solution of 1.0 g (1.84 mmol) of 10deacetylbaccatin III in 50 ml of THF was added 0.857 ml (2.76 mmol, 1.5 equivalents mol) of N, O- (6hc) TES-trifluoroacetamide over a period of 3 min at -10 ° C under nitrogen atmosphere . Then 0.062 ml of 0.89 M solution of THF and lithium bis (trimethylsilyl) amide (0.055 mmol, 0.03 equivalent mol) were added. After 10 min, 0.038 ml (0.92 mmol, 0.5 equivalent mol) of methanol were added and after another 5 min 4 ml (0.055 mmol, 0.03 equivalent mol) of acetic acid were added. The solution was diluted with 300 ml of ethyl acetate and washed twice with 100 ml of saturated aqueous sodium bicarbonate solution. The combined aqueous layers were extracted with 100 ml of ethyl acetate, and the combined organic layers were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. 100 ml of hexane was added to the residue and the solid (1.23 g, 101%) was collected by filtration. Recrystallization of the solid by dissolving in boiling ethyl acetate (20 ml, 17 ml / g) and cooling to room temperature to obtain 1.132 g (94%) of a white solid. Mp 242 ° C; [alpha] ₀ ²⁵ - 60.4 (c 0.7, CHCl ₃ ); Ή NMR (CDCl ₃ , 400MHz) δ (pp m): 8.10 (2H, d, Jm = 7.5Hz, Bzo), 7.60 (1H, t, Jm = 7.5Hz, Bzp), 7.47 (2H, t, Jo = 7.5Hz, Bzm), 5.64 (1H, d, J3 = 6.9Hz, H2), 5.26 (1H, s, H10), 4.97 (1H, dd, J66era = 2.2Hz, 16alpha = 9.9Hz, H5), 4.85 ( 1H, dd, JI 4alpha = 8.9Hz, L4beta = 8.9Hz, H13), 4.30 (1H, d, J206eTa = 8.5Hz, H20alpha), 4.23 (1H, ddd, J7OH = 4.5Hz, 16alpha = 6.6Hz, J66eTa = 11.0Hz, H7), 4.15 (1H, d, 120alpha = 8.5Hz, H2Obeta), 4.00 (1H, d, J2 = 6.9Hz, H3), 2.58 (1H, ddd, J7 = 6.6Hz, J5 = 9.9Hz, J66eTa = 14.5Hz, Nbalpha), 2.28-2.25 (5H, m, 4Ac, H14alpha, H14beta), 2.02 (3H, s, 18Me), 1.97 (1H, d, J7 = 4.5Hz, H7OH), 1.78 (1H. ddd, J7 = 11.0Hz, J5 = 2.2Hz, 16alpha = 14.5Hz, Nbeta), 1.68 (3H, s,

19Me), 1.56 (1H, s, 0H1), 1.32 (1H, d, J13 = 8.8Hz, OH13), 1.18 (3H, s, 17Me), 1.06 (3H, s, 16Me), 0.98 (9H, t. JCH ₂ (TES) = 7.3 Hz, CH / TES), 0.65 (6H, dq, JCH ₃ (IES) = 7.3 Hz, CH ₂ (TES)).

10-triethylsilyl-10-deacetyl-7-propionylbaccatin III. To a solution of 1.0 g (1.517 mmol) of 10-triethylsilyl-10-deacetylbaccatin III and 37.0 mg (0.303 mmol) of DMAP in 20 ml of dichloromethane were added 0.920 ml (11.381 mmol) and 0.329 ml (3.794 mmol, 2.5 equivalent mol) of propionyl chloride at room temperature. , in a nitrogen atmosphere, in the order of enumeration. The mixture was stirred at room temperature for 6 h, diluted with 350 ml of ethyl acetate and extracted with 50 ml of 10% aqueous copper sulfate solution. The organic layer was washed with 50 ml of saturated aqueous sodium bicarbonate solution, 50 ml of brine, dried over sodium sulfate and concentrated under reduced pressure. The crude product was dissolved in 75 ml of ethyl acetate, 100 mg of Norit A was added, the mixture was filtered through celite and concentrated under reduced pressure to give 1.13 g of material. Recrystallization of ethyl acetate / hexanes (dissolved in 6.5 ml of decanted ethyl acetate, followed by the addition of 24 ml of hexanes, allowed to cool to room temperature and left to stand for 17 h) gave 787 mg (72.5%) of a white crystalline solid. A second recrystallization (ca340 mg of material dissolved in 2 ml of decanted ethyl acetate, then added 10 ml of hexanes, allowed to cool to room temperature and left to stand for 17 h) gave 181 mg (16.7%) of a white crystalline solid. The combined yield after recrystallization is 89.2%. Mp 129 ° C; [alpha] ₀ ²⁵ - 47.9 (c 1.0, CHCl ₃ ); NMR Ή (CDCl ₃ , 300MHz) δ (ppm): 8.10 (2H, d, Jm = 7.4Hz, Bzo), 7.60 (1H, t, Jm = 7.4Hz, Bzp), 7.48 (2H, dd, Jo = 7.4 Hz, Jp = 7.4Hz, Bzm), 5.64 (1H, d, J3 = 7.4Hz, H2), 5.47 (1H, dd, 16alpha = 7.4Hz, J66era = 10.1Hz, H7), 5.28 (1H, s, H10) ), 4.94 (1H, d, 16alpha = 9.4Hz, H5), 4.80-4.90 (1H, m, H13), 4.31 (1H, d, J206era = 8.1Hz, H20alpha) 4.16 (1H, d, 120alpha = 8.1Hz , H20beta), 4.06 (1H, d, J2 = 7.4Hz, H3), 2.55 (1H, ddd, J7 = 7.4Hz, J5 = 9.4Hz, J66eTa = 14.8Hz, Nbalfa), 2.28 (3H, s, 4Ac) , 2.23-2.32 (4H, m, 7CH ₂ N14alfa, N14beta, 2.07 (H, s, 18Me), 2.02 ( 1H, d, EW = 4.7Hz, ON13), 1.76-1.87 (4H, m, Nbbeta, 19Me ), 1.60 (1H, s, ON1), 1.17 (H, s, 17Me), 1.09 (H, t, J7CH ₂ - 7.4Hz, 7SN _3), 1.04 (H, s, 16Me), 0.96 (9H, t , JCH ₂ (TES) = 8.0Hz, CH ₃ (IES)), 0.52-0.62 (6H, m, CH ₂ (TES)).

2'-O-MOP-3'-desphenyl-3 '- (2-furyl) -10-triethylsilyl-7-propionyl taxotere.

To a solution of 493 mg (0.690 mmol) of 10-triethylsilyl-10-deacetyl-7-propionylbaccatin III in 4 ml of anhydrous THF was added 0.72 ml (0.72 mmol) of a 1M solution of LiHMDS in THF under nitrogen atmosphere at -45 ° C. After 0.5 h 263 mg (0.814 mmol) of beta-Lactam solution (previously dried as described above) was added in 2 ml of anhydrous THE The mixture was warmed to 0 ° C and after 2 h 0.5 ml of saturated aqueous solution was added. of sodium bicarbonate. The mixture was diluted with 50 ml of ethyl acetate and washed twice with 5 ml of brine. The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give 742 mg (104%) of a pale yellow solid. The solid was recrystallized by dissolving it in 12 ml of a 1: 5 mixture of ethyl acetate and hexane at reflux temperature, and then cooled to room temperature to obtain 627 mg (88%) of a white crystalline solid. The mother liquor was evaporated to give 96 mg of material which was recrystallized as described above from a 2 ml 1: 5 mixture of ethyl acetate and hexane to give an additional 46 mg (6%) of a white crystalline solid. The total recrystallization yield is 94%. The mother liquor was evaporated to give 46 mg of material which was purified by chromatography on a silica gel column to give an additional 20 mg (3%) of product. Mp 207-209 ° C; [a] _D ²⁵ -30.0 (c 5.0, methanol); 1 H NMR (CDCl ₃ , 400 MHz) d (ppm): 8.098.11 (m, 2H), 7.58-7.61 (m, 1H), 7.47-7.51 (m, 2H), 7.39 (d, J = 0.8 Hz. 1H), 6.34 (dd, J = 3.2,1.6 Hz, 1H), 6.26 (d, J = 3.2 Hz), 6.14 (dd, J = 8.8, 8.8 Hz, 1H), 5.71 (d, J = 6.8 Hz). 1H), 5.47 (dd, J = 10.0,7.2 Hz, 1H), 5.30-5.36 (m, 2H), 5.28 (s, 1H), 4.95 (d, J - 7.6 Hz, 1H), 4.76 (s, 1H) ), 4.33 (d, J = 8.0 Hz, 1H),

4.19 (d, J = 8.4 Hz, 1H), 4.03 (d, J = 6.8 Hz, 1H), 2.83 (s, 3H), 2.55 (ddd, J = 17.2, 9.6, 7.6, 1H), 2.50 (s. 3H), 2.20-2.40 (m, 2H), 2.28 (q, J = 7.6 Hz, 2H), 1.95 (s, 3H), 1.84 (ddd, J = 14.8,10.8,2H), 1.80 (s, 3H) , 1.67 (s, 1H), 1.39 (s, 9H), 1.32 (s, 3H), 1.21 (s, 3H), 1.20 (s, 3H), 1.74 (s, 3H), 1.09 (t, J = 7.6). Hz, 3H), 0.93-0.99 (m, 9H), 0.50-0.65 (m, 6H).

3'-Desphenyl-3 '- (2-furyl) -7-propionyltaxoter. (1393) To a solution of 206 mg (0.199 mmol) of 2'-O-MOP-3'-desphenyl-3 '- (2-furyl) -Utryethylsilyl-7-propionyltaxoter in 1.7 ml of pyridine and 5.4 ml of acetonitrile was added 0.80 ml (2.0 mmol) aqueous solution containing 49% HF at 0 ° C. The mixture was warmed to room temperature for 14 h, then diluted with 20 ml of ethyl acetate and washed three times with 2 ml of saturated aqueous sodium bicarbonate solution; and then with 8 ml of brine. The organic phase was dried over sodium sulfate and concentrated under reduced pressure to give 170 mg (100%) of a white solid. The crude product was crystallized with 2 ml of solvent (CH ₂ Cl ₂ : hexane = 1: 1.7) to give 155 mg (90.5%) of white crystals. The mother liquor was concentrated under reduced pressure to give 15 mg of material, which was recrystallized from 0.2 ml of a 1: 1.7 mixture of methylene chloride and hexane to give an additional 11 mg (7.5%) of white crystals. The total recrystallization yield is 98%. Mp 150-152 ° C; [a] _D ²⁵ -27.0 (c 5.0, methanol); Analysis. Calc. for C ^ H ^ NO ^. 0.5 H ₂ O: C, 61.18;

H, 6.48. Found: C, 61.40; H, 6.65. Ή NMR (CDCl ₃ , 500 MHz) d (ppm): 8.11 (d, J = 7.5 Hz, 2H),

7.61 (dd, J = 7.5.7.5 Hz, 1H), 7.50 (dd, J = 8.0.7.5 Hz, 2H), 7.41 (d, J = 1.0 Hz, 1H), 6.38 (dd, J = 3.0, 2.0 Hz) , 1H), 6.33 (d, J = 3.5 Hz), 6.22 (dd, J = 9.5,

9.5 Hz, 1H), 5.69 (d, J = 7.0 Hz, 1H), 5.49 (dd, J = 11.0,7.5 Hz, 1H), 5.35 (d, J = 9.5 Hz, 1H), 5.33 (d, J = 1.5 Hz, 1H), 5.25 (d, J = 9.5 Hz, 1H), 4.94 (d, J = 8.5 Hz, 1H), 4.71 (dd, J = 5.5, 2.0 Hz, 1H), 4.33 (d, J = 8.5 Hz, 1H), 4.21 (d, J = 8.5 Hz, 1H), 4.01 (d, J = 6.5 Hz, 1H), 3.97 (d, J = 1.5 Hz, 1H), 3.30 (d, J = 5.5 Hz) , 1H), 2.54 (ddd, J = 16.5, 9.5, 7.0, 1H), 2.41 (s, 3H), 2.37 (dd, J = 15.0, 9.0 Hz, 1H), 2.30 (dd, J = 17.5,9.5 Hz) , 1H), 2.25 (q, J = 7.5 Hz, 2H),

I. 96 (s, 3H), 1.93 (ddd, J = 14.5,11.0,2.5 Hz), 1.85 (s, 3H), 1.64 (s, 1H), 1.36 (s, 9H), 1.23 (s, 3H) , 1.10 (t, J = 7.5 Hz, 3H).

Example 2.

The processes described in Example 1 were carried out, but the beta-lactam of Example 1 was replaced by other suitably protected beta-lactams to give a series of compounds of structural formula (13), and combinations of substituents are given in the following table:

Composition Xs Hz R? 1351 tBuOCO- ibue EtCOO- 1364 tBuOCO- 2-pyridyl EtCOO- 1372 tBuOCO- 3-Pyridyl EtCOO- 1386 tBuOCO- 4-Pyridyl EtCOO- 1393 tBuOCO- 2-furyl EtCOO- 1401 tBuOCO- 3-furyl EtCOO- 1418 tBuOCO- 2-thienyl EtCOO- 1424 tBuOCO- 3-thienyl EtCOO- 1434 tBuOCO- isopropyl EtCOO- 1447 tBuOCO- cyclobutyl EtCOO- 1458 tBuOCO- phenyl EtCOO- 3069 2FuCO- 2-thienyl EtCOO- 3082 iPrOCO- 2-thienyl EtCOO- 3171 NPrCO- 2-furyl EtCOO- 3196 iBuOCO- 2-furyl EtCOO- 3232 iBuOCO- 2-thienyl EtCOO- 3327 nPrCO- 2-thienyl EtCOO- 3388 PhCO- 3-thienyl EtCOO- 3444 iPrOCO- 2-furyl EtCOO- 3479 2-ThCO- 2-thienyl EtCOO- 3555 C ₄ H ₇ CO- 2-thienyl EtCOO- 3560 tC ₃ H ₅ CO- 2-thienyl EtCOO- 3611 EtOCO- 2-furyl EtCOO- 3629 2-FuCO- 2-furyl EtCOO- 3632 2-ThCO- 2-furyl EtCOO- 3708 tC ₃ H ₅ CO- 2-furyl EtCOO- 3713 C4H7CO- 2-furyl EtCOO- 4017 PhCO- 2-furyl EtCOO- 4044 EtOCO- 2-thienyl EtCOO- 4106 3-PyCO- 2-thienyl EtCOO- 4135 iPrOCO- 2-thienyl PrCOO- 4175 PhCO- 2-thienyl PrCOO- 4219 2-FuCO- 2-thienyl PrCOO- 4256 tBuOCO- 2-thienyl PrCOO- 4283 ibueCO- 2-thienyl PrCOO- 4290 iBuOCO- 2-thienyl PrCOO- 4312 ibueCO- 2-thienyl EtCOO- 4388 2-ThCO- 2-thienyl PrCOO- 4394 tBuOCO- 3-furyl PrCOO- 4406 tBuOCO- isobutene PrCOO-

4446 tBuOCO- 3-thienyl PrCOO- 4499 tBuOCO- 2-furyl PrCOO- 4544 iBuOCO- 3-thienyl PrCOO- 4600 iBuOCO- 3-thienyl PrCOO- 4616 iBuOCO- 2-furyl PrCOO- 4737 tC ₃ H ₅ CO- 2-furyl PrCOO- 4757 tC ₃ H ₅ CO- 2-thienyl PrCOO- 6171 ibueOCO- 2-furyl .............. EtCOO- 6131 ibueOCO- 2-furyl iBuCOO- 5989 ibueOCO- 2-furyl iPrCOO- 6141 ibueOCO- 2-furyl nBuCOO- 6181 ibueOCO- 2-furyl nPrCOO- 6040 iBuOCO- 2-furyl ibueCOO- 6121 iBuOCO- 2-furyl iPrCOO- 6424 tAmOCO- 2-furyl EtCOO- 6212 tAmOCO- 2-furyl EtCOO- 6282 tAmOCO- 2-furyl iBuCOO- 6252 tAmOCO- 2-furyl iPrCOO- 6343 tAmOCO- 2-furyl nBuCOO- 6272 tAmOCO- 2-furyl nPrCOO- 6202 tC ₃ H _with CO- 2-furyl iPrCOO- 4454 2-ThCO- 2-thienyl nPrCOO- 4414 PhCO- 2-thienyl nPrCOO- 6333 tBuOCO- 2-thienyl iPrCOO- 6686 tBuOCO- 2-thienyl tC ₃ H ₅ COO- 6363 tBuOCO- 2-thiazole EtCOO- 4787 iBuOCO- 3-furyl EtCOO- 4828 iBuOCO- 3-furyl nPrCOO- 4898 tC ₃ H ₅ CO- 3-furyl EtCOO- 4939 tC ₃ H ₅ CO- 3-furyl nPrCOO- 5020 tC ₃ HsCO- 3-thienyl EtCOO- 5030 tC ₃ H ₅ CO- 3-thienyl nPrCOO- 5191 iBuOCO- srgo EtCOO- 5202 iBuOCO- srgo nPrCOO- 5070 tBuOCO- srgo EtCOO- 5080 tBuOCO- srgo nPrCOO- 5121 iBuOCO- ibue EtCOO- 5131 iBuOCO- ibue nPrCOO-

Example 3.

Following the processes described in Example 1, and throughout the text, the following specific taxanes of structural formula 14 can be obtained, where it has the meaning defined above, including where R ₇ represents R _{? A} COO- and R, _a represents (i) a substituted or unsubstituted C ₂ to C ₈ alkyl (straight, branched or cyclic) group such as ethyl, propyl, butyl, pentyl or hexyl; (n) substituted or unsubstituted C ₂ to C _g alkenyl (straight, branched or cyclic) group such as ethenyl, propenyl, butenyl, pentenyl or hexenyl; (iii) a substituted or unsubstituted C to C apinyl (straight or branched) group such as an ethynyl group, propynyl group, butynyl group, pentynyl or hexynyl group; (iv) a substituted or unsubstituted phenyl group; or (ν) a substituted or unsubstituted heteroaromatic group such as a furyl 5 group, a thienyl or a pyridyl group.

The substituents may be hydrocarbyl groups or any heteroatom-containing substituent selected from a heterocyclo group, an alkoxy group, an alkoxy group, an alkoxy group, an aryloxy group, a 10 hydroxy group, a protected hydroxy group, a keto group, an acyloxy group, a nitro group, an amino group, an amido group, thiol group, ketal group, acetal group, ester and ether moieties, but not containing phosphorus moieties.

(14)

X ₅ Hz r ₇ tBuOCO- 2-furyl R, COO- tBuOCO- 3-furyl RaCOO- tBuOCO- 2-thienyl RaCOO- tBuOCO- 3-thienyl RaCOO- tBuOCO- 2-pyridyl RaCOO-

tBuOCO- 3-Pyridyl R _a COO- tBuOCO- 4-Pyridyl R _a COO- tBuOCO- isobutene RaCOO- tBuOCO- isopropyl RaCOO- tBuOCO- cyclopropyl RaCOO- tBuOCO- cyclobutyl RaCOO- tBuOCO- cyclopentyl RaCOO- tBuOCO- phenyl RaCOO- benzoyl 2-furyl RaCOO- benzoyl 3-furyl RaCOO- benzoyl 2-thienyl RaCOO- benzoyl 3-thienyl RaCOO- benzoyl 2-pyridyl RaCOO- benzoyl 3-Pyridyl RaCOO- benzoyl 4-Pyridyl RaCOO- benzoyl isobutene RaCOO- benzoyl isopropyl RaCOO- benzoyl cyclopropyl RaCOO- benzoyl cyclobutyl RaCOO- benzoyl cyclopentyl RaCOO- benzoyl phenyl RaCOO- 2-FuCO- 2-furyl RaCOO- 2-FuCO- 3-furyl RaCOO- 2-FuCO- 2-thienyl RaCOO- 2-FuCO- 3-thienyl RaCOO- 2-FuCO- 2-pyridyl RaCOO- 2-FuCO- 3-Pyridyl RaCOO- 2-FuCO- 4-Pyridyl RaCOO- 2-FuCO- isobutene RaCOO- 2-FuCO- isopropyl RaCOO- 2-FuCO- cyclopropyl RaCOO- 2-FuCO- cyclobutyl RaCOO- 2-FuCO- cyclopentyl RaCOO- 2-FuCO- phenyl RaCOO- 2-ThCO- 2-furyl RaCOO- 2-ThCO- 3-furyl RaCOO- 2-ThCO- 2-thienyl RaCOO- 2-ThCO- 3-thienyl RaCOO- £ -ThCO- 2-pyridyl RaCOO- 2-ThCO- 3-Pyridyl RaCOO- 2-ThCO- 4-Pyridyl RaCOO- 2-ThCO- isobutene RaCOO- 2-ThCO- isopropyl RaCOO- 2-ThCO- cyclopropyl RaCOO- 2-ThCO- cyclobutyl RaCOO- 2-ThCO- cyclopentyl RaCOO- 2-ThCO- phenyl RaCOO- 2-PyCO- 2-furyl RaCOO- 2-PyCO- 3-furyl RaCOO- 2-PyCO- 2-thienyl RaCOO-

2-Ruso- 3-thienyl ReCOO- 2-Ruso- 2-pyridyl R _a COO- 2-Ruso- 3-Pyridyl RaCOO- 2-Ruso- 4-Pyridyl RaCOO- 2-Ruso- isobutene RaCOO- 2-Ruso- isopropyl RaCOO- 2-Ruso- cyclopropyl RaCOO- 2-Ruso- cyclobutyl RaCOO- 2-Ruso- cyclopentyl RaCOO- 2-Ruso- phenyl RaCOO- 3-Ruso- 2-furyl RaCOO- 3-Ruso- 3-furyl RaCOO- 3-Ruso- 2-thienyl RaCOO- 3-Ruso- 3-thienyl RaCOO- 3-Ruso- 2-pyridyl RaCOO- 3-Ruso- 3-Pyridyl RaCOO- 3-Ruso- 4-Pyridyl RaCOO- 3-Ruso- isobutene RaCOO- 3-Ruso- isopropyl RaCOO- 3-Ruso- cyclopropyl RaCOO- 3-Ruso- cyclobutyl RaCOO- 3-Ruso- cyclopentyl RaCOO- 3-Ruso- phenyl RaCOO- 4-Ruso- 2-furyl RaCOO- 4-Ruso- 3-furyl RaCOO- 4-Ruso- 2-thienyl RaCOO- 4-Ruso- 3-thienyl RaCOO- 4-Ruso- 2-pyridyl RaCOO- 4-Ruso- 3-Pyridyl RaCOO- 4-Ruso- 4-Pyridyl RaCOO- 4-Ruso- isobutene RaCOO- 4-Ruso- isopropyl RaCOO- 4-Ruso- cyclopropyl RaCOO- 4-Ruso- cyclobutyl RaCOO- 4-Ruso- cyclopentyl RaCOO- 4-Ruso- phenyl RaCOO- C4H7CO- 2-furyl RaCOO- C4H7CO- 3-furyl RaCOO- C4H7CO- 2-thienyl RaCOO- C4H7CO- 3-thienyl RaCOO- C4H7CO- 2-pyridyl RaCOO- C4H7CO- 3-Pyridyl RaCOO- C ₄ H ₇ CO- 4-Pyridyl RaCOO- C4H7CO- isobutene RaCOO- C4H7CO- isopropyl RaCOO- C4H7CO- cyclopropyl RaCOO- C4H7CO- cyclobutyl RaCOO- C4H7CO- cyclopentyl RaCOO- C4H7CO- phenyl RaCOO- EtOCO- 2-furyl RaCOO-

EtOCO- 3-furyl R _a COO- EtOCO- 2-thienyl RaCOO- EtOCO- 3-thienyl RaCOO- EtOCO- 2-pyridyl RaCOO- EtOCO- 3-Pyridyl RaCOO- EtOCO- 4-Pyridyl RaCOO- EtOCO- isobutene RaCOO- EtOCO- isopropyl RaCOO- EtOCO- cyclopropyl RaCOO- EtOCO- cyclobutyl RaCOO- EtOCO- cyclopentyl RaCOO- EtOCO- phenyl RaCOO- ibueCO- 2-furyl RaCOO- ibueCO- 3-furyl RaCOO- ibueCO- 2-thienyl RaCOO- ibueCO- 3-thienyl RaCOO- ibueCO- 2-pyridyl RaCOO- ibueCO- 3-Pyridyl RaCOO- ibueCO- 4-Pyridyl RaCOO- ibueCO- isobutene RaCOO- ibueCO- isopropyl RaCOO- ibueCO- cyclopropyl RaCOO- ibueCO- cyclobutyl RaCOO- ibueCO- cyclopentyl RaCOO- ibueCO- phenyl RaCOO- iBuCO- 2-furyl RaCOO- iBuCO- 3-furyl RaCOO- iBuCO- 2-thienyl RaCOO- iBuCO- 3-thienyl RaCOO- iBuCO- 2-pyridyl RaCOO- iBuCO- 3-Pyridyl RaCOO- iBuCO- 4-Pyridyl RaCOO- iBuCO- isobutene RaCOO- iBuCO- isopropyl RaCOO- iBuCO- cyclopropyl RaCOO- iBuCO- cyclobutyl RaCOO- iBuCO- cyclopentyl RaCOO- iBuCO- phenyl RaCOO- iBuOCO- 2-furyl RaCOO- iBuOCO- 3-furyl RaCOO- iBuOCO- 2-thienyl RaCOO- iBuOCO- 3-thienyl RaCOO- iBuOCO- 2-pyridyl RaCOO- iBuOCO- 3-Pyridyl RaCOO- iBuOCO- 4-Pyridyl RaCOO- iBuOCO- isobutene RaCOO- iBuOCO- isopropyl RaCOO- iBuOCO- cyclopropyl RaCOO- iBuOCO- cyclobutyl RaCOO- iBuOCO- cyclopentyl RaCOO-

iBuOCO- phenyl RaCOO- iPrOCO- 2-furyl RaCOO- iPrOCO- 3-furyl RaCOO- iPrOCO- 2-thienyl RaCOO- iPrOCO- 3-thienyl RaCOO- iPrOCO- 2-pyridyl RaCOO- iPrOCO- 3-Pyridyl RaCOO- iPrOCO- 4-Pyridyl RaCOO- iPrOCO- isobutene RaCOO- iPrOCO- isopropyl RaCOO- iPrOCO- cyclopropyl RaCOO- iPrOCO- cyclobutyl RaCOO- iPrOCO- cyclopentyl RaCOO- iPrOCO- phenyl RaCOO- nPrOCO- 2-furyl RaCOO- nPrOCO- 3-furyl RaCOO- nPrOCO- 2-thienyl RaCOO- nPrOCO- 3-thienyl RaCOO- nPrOCO- 2-pyridyl RaCOO- nPrOCO- 3-Pyridyl RaCOO- nPrOCO- 4-Pyridyl RaCOO- nPrOCO- isobutene RaCOO- nPrOCO- isopropyl RaCOO- nPrOCO- cyclopropyl RaCOO- nPrOCO- cyclobutyl RaCOO- nPrOCO- cyclopentyl RaCOO- nPrOCO- phenyl RaCOO- nPrCO- 2-furyl RaCOO- nPrCO- 3-furyl RaCOO- nPrCO- 2-thienyl RaCOO- nPrCO- 3-thienyl RaCOO- nPrCO- 2-pyridyl RaCOO- nPrCO- 3-Pyridyl RaCOO- nPrCO- 4-Pyridyl RaCOO- nPrCO- isobutene RaCOO- nPrCO- isopropyl RaCOO- nPrCO- cyclopropyl RaCOO- nPrCO- cyclobutyl RaCOO- nPrCO- cyclopentyl RaCOO- nPrCO- phenyl RaCOO- tBuOCO- cyclopentyl EtCOO- benzoyl 3-furyl EtCOO- benzoyl 2-thienyl EtCOO- benzoyl 2-pyridyl EtCOO- benzoyl 3-Pyridyl EtCOO- benzoyl 4-Pyridyl EtCOO- benzoyl isobutene EtCOO- benzoyl isopropyl EtCOO- benzoyl cyclopropyl EtCOO- benzoyl cyclobutyl EtCOO-

benzoyl cyclopentyl EtCOO- benzoyl phenyl EtCOO- 2-FuCO- C-furyl EtCOO- 2-FuCO- 3-thienyl EtCOO- 2-FuCO- 2-pyridyl EtCOO- 2-FuCO- 3-Pyridyl EtCOO- 2-FuCO- 4-Pyridyl EtCOO- 2-FuCO- isobutene EtCOO- 2-FuCO- isopropyl EtCOO- 2-FuCO- cyclopropyl EtCOO- 2-FuCO- cyclobutyl EtCOO- 2-FuCO- cyclopentyl EtCOO- 2-FuCO- phenyl EtCOO- 2-ThCO- C-furyl EtCOO- 2-ThCO- 3-thienyl EtCOO- 2-ThCO- 2-pyridyl EtCOO- 2-ThCO- 3-Pyridyl EtCOO- 2-ThCO- 4-Pyridyl EtCOO- 2-ThCO- isobutene EtCOO- 2-ThCO- isopropyl EtCOO- 2-ThCO- cyclopropyl EtCOO- 2-ThCO- cyclobutyl EtCOO- 2-ThCO- cyclopentyl EtCOO- 2-ThCO- phenyl EtCOO- 2-PyCO- 2-furyl EtCOO- 2-PyCO- C-furyl EtCOO- 2-PyCO- 2-thienyl EtCOO- 2-PyCO- 3-thienyl EtCOO- 2-PyCO- 2-pyridyl EtCOO- 2-PyCO- 3-Pyridyl EtCOO- 2-PyCO- 4-Pyridyl EtCOO- 2-PyCO- isobutene EtCOO- 2-PyCO- isopropyl EtCOO- 2-PyCO- cyclopropyl EtCOO- 2-PyCO- cyclobutyl EtCOO- 2-PyCO- cyclopentyl EtCOO- 2-PyCO- phenyl EtCOO- 3-PyCO- 2-furyl EtCOO- 3-PyCO- C-furyl EtCOO- 3-PyCO- 3-thienyl EtCOO- 3-PyCO- 2-pyridyl EtCOO- 3-PyCO- 3-Pyridyl EtCOO- 3-PyCO- 4-Pyridyl EtCOO- 3-PyCO- isobutene EtCOO- 3-PyCO- isopropyl EtCOO- 3-PyCO- cyclopropyl EtCOO- 3-PyCO- cyclobutyl EtCOO- 3-PyCO- cyclopentyl EtCOO- 3-PyCO- phenyl EtCOO- 4-PyCO- 2-furyl EtCOO-

4-Ruso- 3-furyl EtCOO-1 4-Ruso- 2-thienyl EtCOO- 4-Ruso- 3-thienyl EtCOO- 4-Ruso- 2-pyridyl EtCOO- 4-Ruso- 3-Pyridyl EtCOO- 4-Ruso- 4-Pyridyl EtCOO- 4-Ruso- isobutene EtCOO- 4-Ruso- isopropyl EtCOO- 4-Ruso- cyclopropyl EtCOO- 4-Ruso- cyclobutyl EtCOO- 4-Ruso- cyclopentyl EtCOO- 4-Ruso- phenyl EtCOO- C ₄ H ₇ CO- 3-furyl EtCOO- C ₄ H ₇ CO- 3-thienyl EtCOO- C ₄ H ₇ CO- 2-pyridyl EtCOO- C ₄ H ₇ CO- 3-Pyridyl EtCOO- C ₄ H ₇ CO- 4-Pyridyl EtCOO- C ₄ H ₇ CO- isobutene EtCOO- C ₄ H ₇ CO- isopropyl EtCOO- C ₄ H ₇ CO- cyclopropyl EtCOO- C ₄ H ₇ CO- cyclobutyl EtCOO- C ₄ H ₇ CO- cyclopentyl EtCOO- C ₄ H ₇ CO- phenyl EtCOO- EtOCO- 3-furyl EtCOO- EtOCO- 3-thienyl EtCOO- EtOCO- 2-pyridyl EtCOO- EtOCO- 3-Pyridyl EtCOO- EtOCO- 4-Pyridyl EtCOO- EtOCO- isobutene EtCOO- EtOCO- isopropyl EtCOO- EtOCO- cyclopropyl EtCOO- EtOCO- cyclobutyl EtCOO- EtOCO- cyclopentyl EtCOO- EtOCO- phenyl EtCOO- ibueCO- 2-furyl EtCOO- ibueCO- 3-furyl EtCOO- ibueCO- 2-thienyl EtCOO- ibueCO- 3-thienyl EtCOO- ibueCO- 2-pyridyl EtCOO- ibueCO- 3-Pyridyl EtCOO- ibueCO- 4-Pyridyl EtCOO- ibueCO- isobutene EtCOO- ibueCO- isopropyl EtCOO- ibueCO- cyclopropyl EtCOO- ibueCO- cyclobutyl EtCOO- ibueCO- cyclopentyl EtCOO- ibueCO- phenyl EtCOO- iBuCO- 2-furyl EtCOO- iBuCO- 3-furyl EtCOO- iBuCO- 2-thienyl EtCOO-

iBuCO- 3-thienyl EtCOO- iBuCO- 2-pyridyl EtCOO- iBuCO- 3-Pyridyl EtCOO- iBuCO- 4-Pyridyl EtCOO- iBuCO- isobutene EtCOO- iBuCO- isopropyl EtCOO- iBuCO- cyclopropyl EtCOO- iBuCO- cyclobutyl EtCOO- iBuCO- cyclopentyl EtCOO- iBuCO- phenyl EtCOO- iBuOCO- 2-pyridyl EtCOO- iBuOCO- 3-Pyridyl EtCOO- iBuOCO- 4-Pyridyl EtCOO- iBuOCO- isobutene EtCOO- iBuOCO- isopropyl EtCOO- iBuOCO- cyclopropyl EtCOO- iBuOCO- cyclobutyl EtCOO- iBuOCO- cyclopentyl EtCOO- iBuOCO- phenyl EtCOO- iPrOCO- 3-furyl EtCOO- iPrOCO- 3-thienyl EtCOO- iPrOCO- 2-pyridyl EtCOO- iPrOCO- 3-Pyridyl EtCOO- iPrOCO- 4-Pyridyl EtCOO- iPrOCO- isobutene EtCOO- iPrOCO- isopropyl EtCOO- iPrOCO- cyclopropyl EtCOO- iPrOCO- cyclobutyl EtCOO- iPrOCO- cyclopentyl EtCOO- iPrOCO- phenyl EtCOO- nPrOCO- 2-furyl EtCOO- nPrOCO- 3-furyl EtCOO- nPrOCO- 2-thienyl EtCOO- nPrOCO- 3-thienyl EtCOO- nPrOCO- 2-pyridyl EtCOO- nPrOCO- 3-Pyridyl EtCOO- nPrOCO- 4-Pyridyl EtCOO- nPrOCO- isobutene EtCOO- nPrOCO- isopropyl EtCOO- nPrOCO- cyclopropyl EtCOO- nPrOCO- cyclobutyl EtCOO- nPrOCO- cyclopentyl EtCOO- nPrOCO- phenyl EtCOO- nPrCO- 3-furyl EtCOO- nPrCO- 3-thienyl EtCOO- nPrCO- 2-pyridyl EtCOO- nPrCO- 3-Pyridyl EtCOO- nPrCO- 4-Pyridyl EtCOO- nPrCO- isobutene EtCOO- nPrCO- isopropyl EtCOO-

prGSO- cyclopropyl EtCOO- prGSO- cyclobugyl EtCOO- prGSO- cyclopentyl EtCOO- prGSO- phenyl EtCOO-

Example 4.

Following the processes described in Example 1, and throughout the text, the following specific taxanes of structural formula 15 can be obtained, wherein R ₁₀ represents a hydroxy group and R ₇ in each series (i.e., each of the series of " A 'to' K ') has the meaning defined above, including where R ₇ represents R 6 COO- and R _{7 a} represents (i) substituted or unsubstituted, preferably 15 unsubstituted, C ₂ to C ₈ alkyl (straight , branched or cyclic) as ethyl, propyl, butyl, pentyl or hexyl; (I) a substituted or unsubstituted, preferably unsubstituted, C ₂ to C ₈ alkenyl 20 (straight, branched or cyclic) group such as ethenyl, propenyl, butenyl, pentenyl or hexenyl; (iii) substituted or unsubstituted, preferably unsubstituted, C ₂ to C ₈ alkynyl (straight or branched) group such as ethynyl, propynyl, butynyl, pentynyl or hexynyl; (ΐν) a substituted or unsubstituted, preferably unsubstituted, phenyl group; or (ν) a substituted or unsubstituted, 30 preferably unsubstituted, heteroaromatic group such as a furyl group, a thienyl or a pyridyl group.

In the series of compounds "A", X _{! 0} has the meaning defined throughout the text. Preferably, the heterocyclo group represents a substituted or unsubstituted furyl group, a thienyl or pyridyl group, X ₁₀ represents a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group 40 or a lower alkyl group (eg, a tertiary butyl group) and R? and R ₁₀ have a beta stereochemical configuration.

In the series of compounds "B", X _1o and R _2a are as otherwise as defined herein. Preferably, the heterocyclo group represents a substituted or unsubstituted furyl group, a thienyl or pyridyl group, X ₁₀ represents, preferably, a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group (e.g., a tertiary butyl group) ), R _2a is preferably a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group, and R ₇ and R ₁₀ have a beta stereochemical configuration.

In the series of compounds "C", X ₁₀ and R _9a have the meaning defined throughout the text. Preferably, the heterocyclo group represents a substituted or unsubstituted furyl group, a thienyl or pyridyl group, X _{) O} represents, preferably, a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group (e.g., a tertiary butyl group) , R _9a represents preferably a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group and R _? , and R ₉ and R ₁₀ have a beta stereochemical configuration.

In the D and E series, X ₁₀ has the meaning defined throughout the text. Preferably, the heterocyclo group represents a substituted or unsubstituted furyl group, a thienyl or pyridyl group, X ₁₀ represents a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group (eg, a tertiary butyl group) and R ₇ , and R ₉ (D series only) and R ₁₀ have a beta stereochemical configuration.

In the series of compounds "F", X ₁₀ , R _2a and R _9a have the meaning defined throughout the text. Preferably, the heterocyclo group represents a substituted or unsubstituted furyl group, a thienyl or pyridyl group, X _{) O} represents, preferably, a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group (e.g., a tertiary butyl group) , R _2a is preferably a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group, and R 1 and R _g and R ₁₀ have a beta stereochemical configuration.

In the series of compounds "G", X ₁₀ and have the meaning defined throughout the text. Preferably, the heterocyclo group represents a substituted or unsubstituted furyl group, a thienyl or pyridyl group, X ₁₀ represents, preferably, a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group (eg, a tertiary butyl group). R _2a is preferably a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group, and R ₇ and R ₉ and R ₁₀ have a beta stereochemical configuration.

In the H series, X ₁₀ has the meaning defined throughout the text. Preferably, the heterocyclo group represents a substituted or unsubstituted furyl group, a thienyl or pyridyl group, X ₁₀ represents a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group (e.g., a tertiary butyl group), R _2a represents. preferably, a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group, and R ₇ and R ₁₀ have a beta stereochemical configuration.

In the series of compounds "I", X ₁₀ and R 4 have the meaning defined throughout the text. Preferably, the heterocyclo group represents a substituted or unsubstituted furyl group, a thienyl or pyridyl group, X _{) O} represents, preferably, a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group (e.g., a tertiary butyl group) , R _2a is preferably a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group, and R ₁ and R ₁₀ have a beta stereochemical configuration.

In the series of compounds "J", X ₁₀ and R _2a have the meaning defined throughout the text. Preferably, the heterocyclo group represents a substituted or unsubstituted furyl group, a thienyl or pyridyl group, X ₁₀ represents, preferably, a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group (eg, a tertiary butyl group), R _2a is preferably a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group, and R ₇ and R ₉ and R ₁₀ have a beta stereochemical configuration.

In the series of compounds "K", X ₁₀ , R _2a and R _9a have the meaning defined throughout the text. Preferably, the heterocyclo group represents a substituted or unsubstituted furyl group, a thienyl or pyridyl group, X _{) O} represents, preferably, a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group (e.g., a tertiary butyl group) , R _2a is preferably a substituted or unsubstituted furyl group, a thienyl group, a pyridyl group, a phenyl group or a lower alkyl group, and R ₇ and R ₉ and R ₁₀ have a beta stereochemical configuration.

Any of the substituents X ₃ , X ₅ , R 1, R, and R can be a hydrocarbyl group or any substituent containing a heteroatom selected from a heterocyclo group, alkoxy group, alkenyloxy group, alkyloxy group, aryloxy group, hydroxy group, protected hydroxy group, keto group, acyloxy group, nitro group, amino group, amido group, thiol group, ketap group, acetal group, ester and ether moieties but not containing phosphorus moieties.

The series Xs Hz R7 K ₂ r ₉ R | 4 Al - Sooooh heterocycle R7.COO- CeHjCOO- 0 H A2 -COXio heterocycle R7 _a COO- SbNzOOOO- 0 H i 'I -CONHX _l0 heterocycle R _7B COO- CoHsCOO- 0 H ~ 1 A4 _ - Sooooh substituted or unsubstituted C ₂ -C 8 alkyl group R _7a COO- SbNzOOOO- 0 H A5 1 -COX _{] 0} substituted or unsubstituted C ₂ -C 8 alkyl group R _7a C0O- SbNzOOOO- 0 H A6 -CONHXjo substituted or unsubstituted C 2 - C ₈ alkyl group R7aCOO- SbNzOOOO- 0 H [A7 -COOXio substituted or unsubstituted C ₂ -C 8 alkenyl group R _7a COO- CsHsCOO- 0 h i i A8 -COX ₁₀ substituted or unsubstituted C 2 -C ₈ alkenyl group R7 _a COO- SbNzOOOO- 0 H A9 -CONHXjo substituted or unsubstituted C 2 -C 8 alkenyl group R7 _a COO- SbNzOOOO- 0 H 1 A10 i -COOXio substituted or unsubstituted C 1 -C 8 alkynyl group ^R 7aCOO- SbNzOOOO- 0 H i All -COXio substituted or unsubstituted C2-C8 alkynyl group RlaCOO- SbNzOOOO- 0 H A12 -CONHXio substituted or unsubstituted C 2 - C ₈ alkynyl, R _7a COO- SbNzOOOO- 0 ^H ! Bl -COOX _{! 0} heterocycle R7 _a COO- RTaCOO- 0 H B2 -COXio heterocycle R _7a COO- R2aCOO- 0 H B3 -CONHXjo heterocycle R ₇ .COO- R _2a COO- 0 H and B4 - Sooooh a substituted or unsubstituted C2-C8 alkyl group R7.COO- R2aCOO- 0 H and B5 j______________________________________ I -COXio substituted or unsubstituted C 1 -C 8 alkyl group R _7e COO- RzaCOO- 0 H 1 i i B6 -CONHXjo substituted or unsubstituted C 1 -C 8 alkyl group R _7a COO- R _2a COO- 0 H B7 - Sooooh substituted or unsubstituted C 1 -C 8 alkenyl group R7.COO- RzaCOO- 0 H B8 -COXio substituted or unsubstituted C 2 -C 8 alkenyl group R-7aC00- R2.COO- 0 H B9 -CONHXio substituted or unsubstituted Cg-Cg R _7a COO- RtbCOO- 0 H

alkenyl group BIO - Sooooh substituted or unsubstituted C ₂ -C 8 alkynyl group R7.COO- RiaCOO- 0 H vp -cox ₁₀ substituted or unsubstituted C ₂ - C ₈ alkynyl, R7 ₈ COO- RiaCOO- 0 H 1 B12 -CONHXio substituted or unsubstituted C ₂ -C 8 alkynyl group R _7b COO- RiaCOO- 0 H Cl -COOX ₁₀ heterocycle RiaCOO- C ₆ H ₅ COO- RsaCOO- H C2 - SOHU heterocycle R7 _a COO- SbNzOOOO- RsaCOO- H C3 -CONHXio heterocycle R _7a COO- SbNzOOOO- RsaCOO- H C4 - Sooooh substituted or unsubstituted C ₂ -C ₆ alkyl group R _7a COO- SbNzOOOO- R _9a COO- I H [ 1 C5 I 1 - SOHU substituted or unsubstituted C ₂ -C 8 alkyl group R _7a COO- SbNzOOOO- R _9a COO- H C6 -CONHXjo substituted or unsubstituted C ₂ -C 8 alkyl group R _7a COO- SbNzOOOO- R9 ₈ COO- I H [ C7 - Sooooh substituted or unsubstituted C ₂ -C 8 alkenyl group R _7b COO- SbNzOOOO- R _9b COO- H C8 - SOHU substituted or unsubstituted C ₂ -C ₆ alkenyl group R _7a COO- SbNzOOOO- R9 _a COO- h i 1 1 C9 -CONHXio substituted or unsubstituted C ₂ -C 6 alkenyl group R _7a COO- SbNzOOOO- R _9a COO- H CIO - Sooooh substituted or unsubstituted C ₂ -C ₆ alkynyl group R7 _# COO- SbNzOOOO- RiaCOO- H Cll - SOHU substituted or unsubstituted C ₂ -C 8 alkynyl group R _7a COO- SbNzOOOO- R _9b COO- H C12 -CONHXio substituted or unsubstituted C ₂ -C ₆ alkynyl group R7 _B COO- SbNzOOOO- R _9b COO- H DI - Sooooh heterocycle RiaCOO- SbNzOOOO- OH H D2 - SOHU heterocycle r _7b coo- SbNzOOOO- OH H D3 -CONHXio heterocycle R _7b COO- SbNzOOOO- OH H D4 - Sooooh substituted or unsubstituted C ₂ -C 8 alkyl group r _7b coo- SbNzOOOO- OH H 1 D5 - SOHU substituted or unsubstituted C ₂ -C 8 alkyl group r _7b coo- SbNzOOOO- OH i H 1 D6 -CONHXio substituted or unsubstituted C ₂ -Cg R7 _B COO- CeHsCOO- OH H

an alkyl group D7 -COOXio substituted or unsubstituted C ₂ -C 8 alkenyl group R _7a COO- СБН ₅ СОО- OH H 1 1 D8 -COXjo substituted or unsubstituted C ₂ -C 8 alkenyl group R _7a COO- СБН ₅ СОО- OH H D9 -CONHXio substituted or unsubstituted C ₂ -Cg alkenyl group R7.COO- SbNzOOOO- OH H PART -COOXjo substituted or unsubstituted C ₂ -C 8 alkynyl group R _7a COO- СБН ₅ СОО- OH I 1 H i Dll - SOHU substituted or unsubstituted C ₂ -C 5 alkynyl group R _7a COO- CenSOO- OH H D12 -CONHXio substituted or unsubstituted C ₂ -C 8 alkynyl group R _7a COO- СБН ₅ СОО- OH H; i i and ^E1 -COOXio heterocycle R _7a COO- CeHsCOO- 0 1 OH! E2 - SOHU heterocycle R _7a COO- СБН ₅ СОО- 0 he 1 E3 -CONHXio heterocycle R _7a COO- CoHsCOO- 0 he I E4 -COOX _I0 substituted or unsubstituted C ₂ -C ₆ alkyl group R _7a COO- СБН ₅ СОО- 0 1 OH 1 E5 - SOHU substituted or unsubstituted C ₂ -C 8 alkyl group R _7a COO- СБН ₅ СОО- 0 OH E6 -CONHXio substituted or unsubstituted C ₂ -C 8 alkyl group R _7a COO- СБН ₅ СОО- 0 OH E7 1 -COOXio substituted or unsubstituted C ₂ -C ₆ alkenyl group R _7a COO- СБН ₅ СОО- 0 OH E8 - SOHU substituted or unsubstituted C ₂ -C ₆ alkenyl group R _7a COO- SbNzOOOO- 0 OH i E9 -CONHXio substituted or unsubstituted C ₂ -C 8 alkenyl group R _7a COO- СБН ₅ СОО- 0 i OH i E1O -COOXio substituted or unsubstituted C ₂ - C ₈ alkynyl, R _7a COO- SbNzOOOO- 0 OH Ell - SOHU substituted or unsubstituted C ₂ -C 8 alkynyl group R _7a COO- SLzOO- 0 OH E12 -CONHXio substituted or unsubstituted C ₂ -C _g alkynyl group R _7a COO- СБН ₅ СОО- 0 OH Fl -COOXio heterocycle R _7a COO- R _2a COO- RjaCOO- H F2 -COX ₁₀ heterocycle R _7a COO- R _2a COO- RsaCOO- .Hi

F3 -CONHX ₁₀ heterocycle RvaCOO- R _2a COO- R _9a COO- η | F4 -COOXio substituted or unsubstituted C ₂ -C 8 alkyl group R _7a COO- R _2a COO- R _9a COO- H I 1 F5 - SOHU substituted or unsubstituted C ₂ -C 8 alkyl group R _7a COO- R2aCOO- R _9a COO- H F6 -CONHXio substituted or unsubstituted C ₂ -C 8 alkyl group R _7a COO- R _2a COO- R _9a COO- H; F7 -COOXjq substituted or unsubstituted C 1 -C 8 alkenyl group R _7a COO- R _2a COO- R _9a COO- H i F8 - SOHU substituted or unsubstituted C 1 -C 8 alkenyl group R _7a COO- R _2a COO- R _9a COO- H j 1 F9 -CONHXio substituted or unsubstituted C 2 -C 10 alkenyl group R _7a COO- R _2a COO- R _9a COO- ----------------------------- 1 H F10 -COOXio substituted or unsubstituted C 1 -C 8 alkynyl group R _7a COO- R _2a COO- R _9a COO- H i ΐ F11 ί I 1 -cox _I0 substituted or unsubstituted C 1 -C 8 alkynyl carcase R _7a COO- R _2a COO- R _9a COO- i Η ί 1 F12 -CONHXio substituted or unsubstituted C ₂ -C 5 alkynyl group R _7a COO- R _2a COO- R _9a COO- H G1 -COOXio heterocycle R _7a COO- R _2a COO- OH H G2 - SOHU heterocycle R _7a COO- R _2a COO- OH H G3 -CONHXio heterocycle R _7a COO- R _2a COO- OH H G4 i -COOXio substituted or unsubstituted C 1 -C 8 alkyl group R _7a COO- RiaCOO- OH H 1 G5 ] ________________________________ - SOHU substituted or unsubstituted C 1 -C 8 alkyl group R _7a COO- R _2a COO- OH 1 H! i | G6 -CONHXjo i a substituted or unsubstituted C 1 -C 8 alkyl group R _7a COO- R _2a COO- OH η: ! j f G7 I -COOXio substituted or unsubstituted C 1 -C 8 alkenyl group R _7a COO- R _2a COO- OH ! ^H i G8 -COX ₁₀ substituted or unsubstituted C 1 -C 8 alkenyl group R _7a COO- R _2a COO- OH H ; G9 -CONHXio substituted or unsubstituted C 1 -C 8 alkenyl group R _7a COO- R _2a COO- OH 1 H 1 and GIO -COOXio substituted or unsubstituted Cg-Cg R _7a COO- R _2a COO- OH H

alkynyl group i i Gil -COX _W substituted or unsubstituted C ₂ -C ₆ alkynyl group R _7a COO- R _2a COO- OH H G12 -CONHXio substituted or unsubstituted C 1 -C 5 alkynyl group R _7b COO- R _2a COO- OH H Hl -COOXio heterocycle r _7b coo- CeHsCOO- OH OH H2 -COXio heterocycle R _7a COO- SbNzOOOO- OH OH NZ -CONHXio heterocycle R _7b COO- SbNzOOOO- OH OH H4 -COOX ₁₀ substituted or unsubstituted C ₂ -C 8 alkyl group R _7a COO- SbNzOOOO- OH OH H5 -COXio substituted or unsubstituted C ₂ -C 8 alkyl group R _7a COO- СБН ₅ СОО- OH OH j H6 -CONHXio substituted or unsubstituted C ₂ -C 8 alkyl group R _7a COO- СБН ₅ СОО- OH i OH! i H7 -COOXio substituted or unsubstituted C ₂ -C ₆ alkenyl group R _7b COO- SbNzOOOO- OH OH H8 -COX ₁₀ substituted or unsubstituted C ₂ -C ₆ alkenyl group R _7a COO- СБН ₅ СОО- OH OH H9 -CONHXio substituted or unsubstituted C 2 -C 6 alkenyl group R _7b COO- СБН ₅ СОО- OH OH NU -COOXio substituted or unsubstituted C ₂ -C ₆ alkynyl group R _7b COO- СБН ₅ СОО- OH OH Hll -COXio substituted or unsubstituted C ₂ -C ₆ alkynyl group R _7a COO- СБН ₅ СОО- OH OH H12 -CONHXio substituted or unsubstituted C ₂ -C 5 alkynyl group R _7b COO- СБН ₅ СОО- OH OH II -COOXio heterocycle R _7b COO- R & COO- 0 OH 12 -COXio heterocycle R _7b COO- R2aCOO- 0 OH 13 -CONHXio heterocycle R _7b COO- R _2a COO- 0 OH 14 -COOXio a substituted or unsubstituted C2-C3 alkyl group R _7b COO- RiaCOO- 0 OH 15 -COXio substituted or unsubstituted C ₂ -C ₆ alkyl group R _7b COO- R _2a COO- 0 OH 16 -CONHXio substituted or unsubstituted C ₂ -C ₆ alkyl group r _7b coo- RfcCOO- 0 OH 17 -COOXio substituted or unsubstituted C ₂ -Ca r _7b coo- RzaCOO- 0 OH

alkenyl group 18 -cox _l0 substituted or unsubstituted C ₂ -C ₆ alkenyl group R _7a COO- R _2a COO- 0 OH 19 -CONHXio substituted or unsubstituted C 2 -C 6 alkenyl group R _7a COO- R _2a COO- 0 OH ΐ ON -COOXio substituted or unsubstituted C 1 -C 6 alkynyl group R _7a COO- R _2a COO- 0 OH ' Ill -COXio substituted or unsubstituted C 1 -C 3 alkynyl group R _? aCOO- R _2a COO- 0 OH 112 1 -CONHXjo substituted or unsubstituted C 1 -C 6 alkynyl group R _7a COO- R _2a COO- 0 OH JI -COOXio heterocycle r _7b coo- R _2a COO- OH OH J2 -COXio heterocycle R _7a COO- R _2a COO- OH OH I J3 -CONHXio heterocycle R _7a COO- R _2a COO- OH OH I i 1 ^J4 j -COOXio substituted or unsubstituted C 1 -C 3 alkyl group R _7a COO- R _2a COO- OH I OH Ϊ I i J5 -COXio substituted or unsubstituted C 1 -C 6 alkyl group R _{7 #} COO- R2aCOO- OH OH i J6 -CONHXio a substituted or unsubstituted C 1 -C 8 alkyl group R _7a COO- RzaCOO- OH OH J7 -COOXio substituted or unsubstituted C 2 -C 8 alkenyl group R _7a COO- RzaCOO- OH OH J8 -COX ₁₀ substituted or unsubstituted C 2 -C 10 alkenyl group R _7a COO- R _2a COO- OH OH J9 -CONHXio substituted or unsubstituted C 2 -C 6 alkenyl group R _7a COO- R _2a COO- OH '! OH J1O -COOXio substituted or unsubstituted C 1 -C 6 alkynyl group R _7a COO- R _2a COO- OH OH J Jll -COXio substituted or unsubstituted C2-C3 alkynyl group R _7e COO- R _2a COO- OH OH f 1 J12 -CONHXio substituted or unsubstituted C 1 -C 8 alkynyl group R _7a COO- R _2a COO- OH OH KI -COOXio heterocycle R _7a COO- R _2a COO- RgaCOO- OH K2 -COXio heterocycle R _7a COO- R _2a COO- R _9a COO- OH K3 -CONHXio heterocycle R _7a COO- R _2a COO- R? _a COO- OH K4 -COOXio substituted or unsubstituted C 2 -C 3 R _7a COO- R _2a COO- R _9a COO- OH

an alkyl group K5 -x ₁₀ substituted or unsubstituted C ₂ -C 10 alkyl group R _7a COO- R _2a COO- R _9a COO- OH K6 -CONHXjo substituted or unsubstituted C 1 -C 6 alkyl group R _7a COO- RfcCOO- R _9a COO- OH K7 - Sooooh substituted or unsubstituted C ₂ -C ₆ alkenyl group R _7a COO- R _2a COO- R _9a COO- OH K8 - SOHU substituted or unsubstituted C 2 -C 10 alkenyl group R _7a COO- R _2a COO- R _9a COO- OH K9 -CONHXio substituted or unsubstituted C ₂ -C ₆ alkenyl group R _7a COO- R _2a COO- RgaCOO- OH K10 - Sooooh substituted or unsubstituted C ₂ -C ₈ alkynyl group R _7a COO- R _2a COO- R _9a COO- OH K11 - SOHU substituted or unsubstituted C ₂ -C ₈ alkynyl group R _7a COO- R _2a COO- R _9a COO- OH K12 -CONHXio substituted or unsubstituted C2-C3 alkynyl group r _7s coo- R _2a COO- R _9a COO- OH

Example 5.

In vitro cytotoxicity measured in a cell colony forming assay

Four hundred cells (HCT16) were placed in Petri dishes (60 mm) containing 2.7 ml of medium (McCoy modified 5a medium containing 10% fetal bovine serum and 100 units / ml penicillin and 100 g / ml streptomycin). The cells were incubated in a CO ₂ incubator at 37 ° C for 5 h to attach to the bottom of the Petri dishes. The compounds described in Example 2 were stored in medium at a concentration ten times higher than the final concentration, then 0.3 ml of this stock solution was added to 2.7 ml of medium in the plates. The cells were then incubated with drugs for 72 h at 37 ° C. At the end of the incubation, the media containing the drugs were decanted, the plates were washed with 4 ml of Hank's Balance Salt Solution (HBSS), 5 ml of fresh medium were added and the plates were returned to the incubator to form a colony. Cell colonies were counted using a column counter after 7 days of incubation. Cell survival was calculated and ID50 values (drug concentration causing 50% inhibition of colony formation) were determined for each compound tested.

Composition IN VITRO ID50 (wn) HCT116 taxol 2.1 docetaxel 0.6 1351 <1 1364 <10 1372 2661 1386 <1 1393 <1 1401 <1 1418 <1 1424 <1 1434 <10 1447 <10 1458 <10 3069 <1 3082 <1 3171 <1 3196 <10 3232 <1 3327 <10 3388 <10 3444 <1 3479 <1 3555 <10 3560 <1 3611 <1 3629 <1 3632 <1

Composition IN VITRO ID50 (wn) HCT116 3708 <1 3713 <10 4017 <10 4044 <1 4106 <10 4135 <1 4175 <10 4219 29.0 4256 <1 4283 <1 4290 <10 4312 <1 4388 <1 4394 <1 4406 <1 4446 <1 4499 <1 4544 <10 4600 <10 4616 <1 4737 <1 4757 <1 6171 <10 6131 <1 5989 <10 6141 <1 6181 <1

Composition IN VITRO ID50 (nm) HCT116 6040 <10 6121 <10 6424 21.7 6212 <1 6282 <10 6252 <1 6343 <10 6272 <1 6202 <1 4454 <1 4414 <1 6333 <1 6686 <1 6363 <10 4787 <10 4828 <10 4898 <1 4939 <1 5020 <1 5030 <1 5191 <ίο 5202 <10 5070 <ΐο 5080 <1 5121 21.1 5131 <10

Example 6

Preparation of oral solutions

Solution 1: Antitumor compound 1393 was dissolved in ethanol to give a solution containing 140 mg of the compound per ml of solution. An equivalent volume of Cremophor® EL solution was added to the solution while stirring to obtain a solution containing 70 mg of compound 1393 per ml. The solution thus obtained is diluted with 9 wt. including saline until a pharmaceutically acceptable solution for administration to a patient is obtained.

Solution 2: Antitumor compound 1458 was dissolved in ethanol to give a solution containing 310 mg of the compound per ml of solution. An equivalent volume of Cremophor® EL solution was added to the solution while stirring to obtain a solution containing 155 mg of compound 1458 per ml. The solution thus obtained is diluted with 9 wt. including saline until a pharmaceutically acceptable solution for administration to a patient is obtained.

Solution 3: Antitumor compound 1351 was dissolved in ethanol to give a solution containing 145 mg of the compound per ml of solution. An equivalent volume of Cremophor® EL solution was added to the solution while stirring to obtain a solution containing 72.5 mg of compound 1351 per ml. The solution thus obtained is diluted with 9 wt. including saline until a pharmaceutically acceptable solution for administration to a patient is obtained.

Solution 4: Antitumor compound 4017 was dissolved in ethanol to give a solution containing 214 mg of the compound per ml of solution. An equivalent volume of Cremophor® EL solution was added to the solution while stirring to obtain a solution containing 107 mg of compound 4017 per ml. The solution thus obtained is diluted with 9 wt. including saline until a pharmaceutically acceptable solution for administration to a patient is obtained.

Solution 5: Antitumor compound 1393 was dissolved in 100% ethanol, then mixed with an equivalent volume of Cremophor® EL solution to give a solution containing 70 mg of compound 1393 per ml. The solution thus obtained is diluted with 9 wt. hours D% W (aqueous solution containing 5% by weight dextrose volume) or 0.9% saline solution to obtain a pharmaceutically acceptable solution for patient administration.

Example 7.

Preparation of a suspension containing compound 1393 oral administration

Oral composition of antitumor compound 1393 was obtained by suspending 25 mg of compound 1393 in the form of a fine powder in one ml of vehicle containing 1% carboxymethylcellulose (CMC) in deionized water.

Example 8.

Preparation of a tablet containing compound 1393 oral administration

Antitumor compound 1393 (100 mg) was dissolved in methylene chloride (2 ml) and a solution of Cremophor® EL (100 mg) was added. The methylene chloride was evaporated in vacuo to give a glassy mass. Microcrystalline cellulose (600 mg) was added to the glass mass and mixed to give a powder, which was then treated to give a tablet.

Example 9.

Preparation of emulsions containing compound 1393 for parenteral administration

Emulsion 1: Antitumor compound 1393 was dissolved in 100% ethanol to give a solution containing 40 mg of compound 1393 per ml of solution. The solution thus obtained is diluted by 19 wt. Liposyn® II (20%) stirring to obtain an emulsion containing 2 mg of compound 1393 per ml for parenteral administration.

Emulsion 2: Antitumor compound 1393 was dissolved in 100% ethanol to give a solution containing 40 mg of compound 1393 per ml of solution.

The solution thus obtained is diluted by 19 wt. Liposyn® III (2%) stirring to obtain an emulsion containing 2 mg of compound 1393 per ml for parenteral administration.

Emulsion 3: Antitumor compound 1393 was dissolved in 100% ethanol to give a solution containing 40 mg of compound 1393 per ml of solution. The solution thus obtained is diluted with 9 wt. h. Liposyn® III (2%) stirring to obtain an emulsion containing 4 mg of compound 1393 per ml for parenteral administration.

Example 10.

Preparation of solutions containing compound 1393 for parenteral administration

Solution 1: Antitumor compound 1393 was dissolved in 100% ethanol to give a solution containing 140 mg of compound 1393 per ml of solution. The solution thus obtained was diluted with an equivalent volume of Cremophor® EL solution while stirring, then diluted with 9 wt. h. normal saline to obtain a solution containing 7 mg of compound 1393 per ml solution for parenteral administration.

Solution 2: Antitumor compound 1393 was dissolved in 100% ethanol to give a solution containing 140 mg of compound 1393 per ml of solution. The solution thus obtained was diluted with an equivalent volume of Cremophor® EL solution while stirring, then diluted with 4 wt. hours of normal saline to obtain a solution containing 11.7 mg of compound 1393 per ml solution for parenteral administration.

Solution 3: Antitumor compound 1393 was dissolved in 100% ethanol to give a solution containing 140 mg of compound 1393 per ml of solution. The solution thus obtained was diluted with an equivalent volume of Cremophor® EL solution while stirring, then diluted with 2.33 wt. hours of normal saline to obtain a solution containing 16.2 mg of compound 1393 per ml solution for parenteral administration.

Claims (176)

1. Taxes of formula where R1 is an acyloxy group; R ₇ represents R _7a COO-; _R7a represents a hydrocarbyl group, a substituted hydrocarbyl group, or a heterocyclo group, wherein said hydrocarbyl or substituted hydrocarbyl group contains carbon atoms at the alpha and beta positions relative to the carbon atom linking _Raa ; R1 represents a keto group, hydroxy or acyloxy group; R ₁₀ represents a hydroxy group; R _{14 is a} hydrido or hydroxy group; X ₃ represents a substituted or unsubstituted alkyl group, alkenyl group, alkynyl group or heterocyclo group; X ₅ represents -COX ₁₀ , -COXX _{] O} or -CONHX ₁₀ ; X ₁₀ represents a hydrocarbyl group, a substituted hydrocarbyl group or a heterocyclo group; Ac represents an acetyl group. The taxane according to claim 1, characterized in that the substituent R _? represents a substituted or unsubstituted C ₂ -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. The taxane according to claim 2, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C, - An C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. The taxane according to claim 2, characterized in that X ₃ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl a group, a 3-pyridyl group, a 4-pyridyl group, a C 1 -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group, or X ₅ is -COOX ₁₀ and X _1o represents a substituted or unsubstituted C-C alkyl, C ₂ -C ₈ alkenyl or C ₂ -C ₈ alkynyl. 5. The taxane according to claim 2, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 6. The taxane according to claim 2, wherein R & lt _{; 4} & gt _; represents hydride to a group. 7. The taxane according to claim 6, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C-C _{An 8} alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 8. The taxane according to claim 6, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl a group, a 3-pyridyl group, a 4-pyridyl group, a C 1 -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a substituted or unsubstituted C, - An C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 9. The taxane according to claim 6, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. The taxane according to claim 2, wherein R 1 represents a benzoyloxy group. Taxane according to claim 10, characterized in that X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C _G C _{An 8} alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 12. The taxane according to claim 10, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl a group, a 3-pyridyl group, a 4-pyridyl group, a C ₁ -C 6 alkyl group, a C ₂ -C _g alkenyl group or a C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a substituted or unsubstituted C 1 -C _g an alkyl group, a C ₂ -C _g alkenyl group, or a C ₂ -C ₈ alkynyl group. The taxane according to claim 10, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a tertiary butyl group. 14. The taxane according to claim 2, wherein R ₁₄ represents a hydrido group and R represents a keto group. The taxane according to claim 14, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C A -C ₈ alkyl group, a C ₂ -C _g alkenyl group, or a C ₂ -C ₈ alkynyl group. 16. The taxane of claim 14, characterized in that X ₅ is -COX ₁₀ and _{X] o} is substituted or unsubstituted phenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C ₁ -C ₈ alkyl group, C ₂ -C ₈ alkenyl group or C ₂ -C _g alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents substituted or unsubstituted C- A C 1-6 alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 17. The taxane according to claim 14, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 18. The taxane according to claim 2, wherein R ₂ represents a benzyloxy group and Rg represents a keto group. 19. The taxane according to claim 18, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C A C 1-3 alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 20. The taxane according to claim 18, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl group, 3-pyridyl group, 4 pyridyl group, C ₁ -C ₈ alkyl group, C ₂ -C ₈ alkenyl group or C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents substituted or unsubstituted C 1 -C 6 alkyl a group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 21. The taxane according to claim 18, characterized in that X ₃ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a tert-butyl group. The taxane according to claim 2, wherein R ₁₄ represents a hydrido group and R ₂ represents a benzyloxy group. 23. The taxane according to claim 22, wherein X ₃ represents a 2-furyl group, a 3-furyl group, a 2-thienyl group, a 3-thienyl group, a 2-pyridyl group, a 3-pyridyl group, a 4-pyridyl group, C A -C alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 24. The taxane according to claim 22, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, A 4- pyridyl group, a C 1 -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted C ₁ -C ₆ alkyl group, C ₂ -C ₈ alkenyl group or C ₂ -C ₈ alkynyl group. The taxane according to claim 22, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a tert-butyl group. 26. The taxane according to claim 2, wherein R ₁₄ represents a hydrido group, R represents a keto group and R ₂ represents a benzyloxy group. 27. The taxane according to claim 26, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C 1 -C _{An 8} alkyl group, a C ₂ -C _g alkenyl group or a C ₂ -C ₈ alkynyl group. 28. The taxane according to claim 26, characterized in that X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl a group, a 3-pyridyl group, a 4 pyridyl group, a C 1 -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a substituted or unsubstituted C _t - A C ₈ alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 29. The taxane according to claim 26, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a tertiary butyl group. 30. The taxane according to claim 1, wherein R _7a represents a C ₂ -C ₈ alkyl group. 31. The taxane according to claim 30, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C] - An C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 32. The taxane according to claim 30, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl a group, a 3-pyridyl group, a 4-pyridyl group, a C 1 -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents substituted or unsubstituted C, - An C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 33. The taxane according to claim 30, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a tert-butyl group. The taxane according to claim 30, wherein R ₁₄ is a hydrido group. The taxane according to claim 34, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C, - An C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. The taxane according to claim 34, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl group, 3-pyridyl, 4piridilova group, C _t -C ₈ alkyl, C ₂ -C ₈ alkenyl or C ₂ -C ₈ alkynyl, or X ₅ is _-COOX10 and _X10 is substituted or unsubstituted C, - An C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. The taxane according to claim 34, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a tertiary butyl group. 38. The taxane according to claim 30, wherein R represents a benzyloxy group. 39. The taxane according to claim 38, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C ₍ - An C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 40. A taxane according to claim 38, wherein X ₅ represents COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl, Cj-C ₈ alkyl group, C ₂ -C ₈ alkenyl or C ₂ -C ₈ alkynyl, or X ₅ is -COOX ₁₀ and _{X] 0} is substituted or unsubstituted C _t -C ₈ alkyl group, A C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 41. The taxane according to claim 38, wherein X ₅ represents -COX ₁₀ and 652Ί9 X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X _{| 0} represents a tertiary butyl group. 42. The taxane of claim 30, characterized in that _{R) 4} is hydrido, and R ₉ is keto. 43. The taxane according to claim 42, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C , A -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 44. The taxane of claim 42, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl a group, a 3-pyridyl group, a 4-pyridyl group, a C ₍ -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX _{] O} and X ₁₀ represents a substituted or unsubstituted C 1 - A C ₈ alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 45. The taxane according to claim 42, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 46. The taxane of claim 30, characterized in that Rj is benzoyloxy and R ₉ is keto. 47. The taxane according to claim 46, wherein X ₃ represents a 2 furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3 pyridyl group, 4-pyridyl group, C ₍ - An C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 48. The taxane according to claim 46, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl group, 3-pyridyl group, 4 pyridyl group, C ₍ -C ₈ alkyl group, C ₂ -C ₈ alkenyl group or C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents substituted or unsubstituted Cj-Cj an alkyl group, A C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 49. The taxane according to claim 46, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. The taxane according to claim 30, wherein R ₁₄ represents a hydrido group and R ₂ represents a benzyloxy group. 51. The taxane according to claim 50, characterized in that X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C 1 - An C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 52. The taxane according to claim 50, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl a group, a 3-pyridyl group, a 4-pyridyl group, a C 1 -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents substituted or unsubstituted C 1 -C _{An 8} alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 53. The taxane according to claim 50, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents-COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 54. The taxane according to claim 30, wherein R ₁₄ represents a hydrido group, R ₉ represents a keto group and R ₂ represents a benzyloxy group. 55. The taxane according to claim 54, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C _t - A C ₈ alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ C ₈ alkynyl group. The taxane according to claim 54, wherein X ₅ represents -COXI ₁ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl group, 3-pyridyl group, 4 pyridyl group, C 1 -C ₈ alkyl group, C ₂ -C ₈ alkenyl group or C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents substituted or unsubstituted C 1 A -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 57. The taxane according to claim 54, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a tertiary butyl group. 58. The taxane according to claim 1, wherein _R7a represents an ethyl group. 59. The taxane according to claim 58, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C, - A C ₈ alkyl group, a C ₂ -C _g alkenyl group, or a C ₂ -C ₈ alkynyl group. 60. The taxane according to claim 58, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl a group, a 3-pyridyl group, a 4-pyridyl group, a C 1 -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group or a C 1 -C ₈ alkynyl group or X ₅ represents -COOOX _{] 0} and X ₁₀ represents a substituted or unsubstituted alkyl group , A C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 61. The taxane of claim 58, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 62. The taxane according to claim 58, wherein R ₁₄ is a hydrido group. 63. The taxane according to claim 62, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C] - An C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 64. The taxane according to claim 62, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl a group, a 3-pyridyl group, a 4-pyridyl group, a C 1 -C ₈ alkyl group, a C ₂ -C _g alkenyl group, or a C ₂ -C ₈ alkynyl group or X ₅ represents COOX ₁₀ and X ₁₀ represents substituted or unsubstituted C _{a t-} C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 65. The taxane of claim 62, characterized in that X ₃ is _-COX10 and _X10 is phenyl, or X ₅ is -COOX ₁₀ and _{X] 0} represents a tertiary butyl group. 66. The taxane according to claim 58, wherein R ₂ represents a benzyloxy group. 67. The taxane according to claim 66, characterized in that X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C 1 -C , an alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 68. The taxane according to claim 66, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl a group, a 3-pyridyl group, a 4 pyridyl group, a C 1 -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a substituted or unsubstituted alkyl group , A C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 69. The taxane according to claim 66, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a tertiary butyl group. 70. The taxane according to claim 58, wherein R ₁₄ represents a hydrido group and Rg represents a keto group. 71. The taxane according to claim 70, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C, - A C ₈ alkyl group, a C ₂ -C _g alkenyl group, or a C ₂ -C ₈ alkynyl group. 72. The taxane according to claim 70, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl group, 3-pyridyl group, 4-pyridyl group, C ₁ -C ₈ alkyl group, C ₂ -C ₈ alkenyl group or C ₁ -C alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents substituted or unsubstituted C 1 -C ₈ alkyl group , A C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 73. The taxane according to claim 70, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 74. The taxane according to claim 58, wherein R ₂ represents a benzyloxy group and R represents a keto group. 75. The taxane according to claim 74, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C A C 1-3 alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 76. The taxane according to claim 74, wherein X ₃ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl group, 3-pyridyl group, 4 pyridyl group, C ₁ -C ₈ alkyl group, C ₂ -C ₈ alkenyl group or C ₂ -C ₈ alkynyl group or X ₃ represents -COOOX ₁₀ and X ₁₀ represents a substituted or unsubstituted C 1 -C 6 alkyl group , A C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 77. The taxane according to claim 74, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 78. The taxane of claim 58, characterized in that R _I4 is hydrido, and R ₂ is benzoyloxy. 79. The taxane according to claim 78, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C-C an alkyl group, a C 1 -C alkenyl group, or a C ₂ C alkynyl group. 80. The taxane according to claim 78, wherein X ₃ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl a group, a 3-pyridyl group, a 4-pyridyl group, a C 1 -C 6 alkyl group, a C 1 -C alkenyl group or a C-C ₈ alkynyl group or X ₃ represents -COOOX ₁₀ and X ₁₀ represents a substituted or unsubstituted C 1 -C 6 alkyl group, C A -C alkenyl group or a C-C alkynyl group. 81. The taxane according to claim 78, wherein X ₃ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₃ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 82. The taxane according to claim 58, wherein R ₁₄ represents a hydrido group, Rg represents a keto group and R1 represents a benzyloxy group. 83. The taxane according to claim 82, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C-C an alkyl group, a C 1 -C alkenyl group or a C ₂ C ₈ alkynyl group. 84. The taxane according to claim 82, wherein X ₃ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl a group, a 3-pyridyl group, a 4-pyridyl group, a C 1 -C 4 alkyl group, a C 1 -C alkenyl group or a C-C alkynyl group or X ₃ represents -COOOX ₁₀ and X ₁₀ represents a substituted or unsubstituted C 1 -C 4 alkyl group, a C-C alkenyl group or C 1 -C alkynyl group. 85. The taxane according to claim 82, wherein X ₃ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₃ represents -COX ₁₀ and X ₁₀ represents a tertiary butyl group. 86. The taxane according to claim 82, wherein X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 87. The taxane according to claim 86, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C, - An C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 88. The taxane according to claim 86, wherein X ₃ represents a furyl or thienyl group. 89. The taxane according to claim 86, wherein X ₃ represents a 2-furyl group. 90. The taxane of claim 86, wherein X ₃ represents a 2-thienyl group. 91. The taxane according to claim 86, wherein X ₃ represents a cycloalkyl group. 92. A taxane of the formula wherein it represents a benzoyloxy group; R1 represents R4COO-; R ₁₀ represents a hydroxy group; X ₃ represents a substituted or unsubstituted alkyl group, alkenyl group, alkynyl group or heterocyclo group; X ₅ represents -COX ₁₀ , -COXX ₁₀ or -CONHX ₁₀ ; X ₁₀ represents a hydrocarbyl group, a substituted hydrocarbyl group or a heterocyclo group; and Rj _a is hydrocarbyl, substituted hydrocarbyl, or heterocyclo wherein said hydrocarbyl or substituted hydrocarbyl contains carbon atoms in the alpha and beta positions relative to the carbon atom linking R ^; Ac represents an acetyl group. 93. The taxane according to claim 92, wherein X ₃ represents a 2 furyl group, a 3-furyl group, a 2-thienyl group, a 3-thienyl group, a 2-pyridyl group, a 3-pyridyl group, a 4-pyridyl group, a C 1 -C 8 group. an alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 94. The taxane of claim 93, characterized in that X ₅ is -COX ₁₀ and X _j0 represents a substituted or unsubstituted phenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2piridilova group, 3-pyridyl group, 4 pyridyl group, C ₍ -C ₈ alkyl group, C ₂ -C ₈ alkenyl group or C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents substituted or unsubstituted C 1 -C _{An 8} alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 95. The taxane according to claim 93, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents-COOX ₁₀ and X ₁₀ represents a tertiary butyl group. 96. The taxane according to claim 92, wherein X ₃ represents a furyl or thienyl group. 97. The taxane according to claim 96, wherein X ₅ represents -COX ₁₀ and X ₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2- pyridyl group, 3-pyridyl group, 4-pyridyl group, C 1 -C 8 alkyl group, C ₂ -C ₈ alkenyl group or C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX _{] O} and X ₁₀ represents substituted or unsubstituted C A -Cg alkyl group, a C ₂ -C _g alkenyl group, or a C ₂ -C ₈ alkynyl group. 98. The taxane according to claim 96, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOX ₁₀ and X ₁₀ represents a tertiary butyl group. 99. The taxane according to claim 93, wherein X ₃ represents a cycloalkyl group. 100. The taxane according to claim 99, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl a group, a 3-pyridyl group, a 4-pyridyl group, a C ₁ -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents substituted or unsubstituted C 1 -C _{An 8} alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 101. The taxane according to claim 99, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 102. The taxane according to claim 93, wherein X ₃ represents an isobutenyl group. Taxane according to claim 102, characterized in that X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl a group, a 3-pyridyl group, a 4-pyridyl group, a C 1 -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents substituted or unsubstituted C, - An C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 104. The taxane according to claim 102, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COXX ₀ and X ₁₀ represents a tertiary butyl group. 105. The taxane according to claim 92, characterized in that it represents an ethyl or propyl group. 106. The taxane according to claim 105, wherein X ₃ represents a 2 furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3 pyridyl group, 4-pyridyl group, C] - An C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 107. Taxane according to claim 106, characterized in that X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4 pyridyl group, C 1 -C ₈ alkyl group, C ₂ -C ₈ alkenyl group or C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X _{| 0} represents substituted or unsubstituted A C 1 -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 108. The taxane according to claim 106, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents-COX ₁₀ and X ₁₀ represents a tertiary butyl group. 109. The taxane according to claim 105, wherein X ₃ represents a furyl or thienyl group. 110. The taxane according to claim 109, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl group, 3-pyridyl, 4piridilova group, an alkyl group, a C ₂ -C ₈ alkenyl or C ₂ -C ₈ alkynyl, or X ₅ is -COOX ₁₀ and X _1o represents a substituted or unsubstituted _{(C 8} alkyl group, A C ₂ -C ₈ alkenyl group or a C ₂ -C _g alkynyl group. 111. The taxane according to claim 109, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 112. The taxane according to claim 105, wherein X ₃ represents a cycloalkyl group. Taxane according to claim 112, characterized in that X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 pyridyl a group, a 3-pyridyl group, a 4-pyridyl group, a C 1 -C ₈ alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents substituted or unsubstituted C, - An C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. Taxane according to claim 112, characterized in that X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a tertiary butyl group. 115. The taxane according to claim 105, wherein X ₃ is an isobutenyl group. 116. Taxane according to claim 115, characterized in that X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C ₁ -C ₈ alkyl group, C ₂ -C ₈ alkenyl group or C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents substituted or unsubstituted C 1 -C ₈ an alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 117. The taxane of claim 115, characterized in that X ₅ is -COX ₁₀ and X ₁₀ is phenyl, or X ₅ is -COOX ₁₀ and _{X) 0} is t-butyl. 118. Taxane according to claim 92, characterized in that X ₃ represents a furyl or thienyl group, 1 C represents ethyl group and X ₅ represents -COX ₁₀ and X ₁₀ represents phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents tertiary butyl group. 119. The taxane of claim 92 wherein _X3 is substituted or unsubstituted furyl group, represents an ethyl group and X ₅ is _{-COX) 0} and _{X] 0} represents a phenyl group, or X ₅ is -COOX ₁₀ and X ₁₀ represents a tertiary butyl group. 120. The taxane according to claim 92, wherein X ₃ represents a substituted or unsubstituted thienyl group, R _? represents an ethyl group and X ₅ represents -COX ₁₀ and X represents a phenyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a tert-butyl group. Taxan according to claim 92, characterized in that X ₃ represents an isobutenyl group, 1 C represents an ethyl group and X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group . 122. The taxane according to claim 92, wherein X ₃ represents an alkyl group, R _7a represents an ethyl group and X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX _{) 0} and X ₁₀ represents tertiary butyl group. 123. The taxane according to claim 92, wherein X ₃ represents a 2-furyl or 2-thienyl group, R _7a represents an ethyl group, X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 124. Taxane, characterized in that X ₃ represents a 2-furyl group, R _7a represents ethyl group, X ₅ represents -COOOX ₁₀ and X ₁₀ represents a butyl group according to claim 92. 125. The taxane according to claim 92, wherein X ₃ represents a 2-thienyl group, R _7a represents an ethyl group, X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 126. The taxane according to claim 92, wherein X ₃ represents an isobutynyl group, X ₅ represents -COOOX ₁₀ and X ₁₀ represent a butyl group. 127. The taxane of claim 92 wherein _X3 is cycloalkyl, R _7a is ethyl, X _{5 is-SOOH] 0} and _X10 is t-butyl. 128. A pharmaceutical composition comprising a taxane according to claim 1 and at least one pharmaceutically acceptable carrier. 129. A pharmaceutical composition according to claim 128, wherein X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C- A C 1-6 alkyl group, a C ₂ -C ₈ alkenyl group or a C ₂ -C ₈ alkynyl group. 130. A pharmaceutical composition according to claim 129 wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2- pyridyl group, 3 pyridyl group, 4-pyridyl group, C ₁ -C ₈ alkyl group, C ₂ -C ₈ alkenyl group or C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents substituted or unsubstituted C-C ₈ an alkyl group, a C ₂ -C _g alkenyl group, or a C ₂ -C ₈ alkynyl group. 131. The pharmaceutical composition of claim 129, characterized in that X ₅ is -COX ₁₀ and X ₁₀ is phenyl, or X ₅ is -COOX ₁₀ and _{X] 0} represents a tertiary butyl group. 132. A pharmaceutical composition according to claim 128, wherein R _7a represents an ethyl or propyl group. Pharmaceutical composition according to claim 132, characterized in that X ₃ represents a 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C 2 - A C8 alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. 134. A pharmaceutical composition according to claim 133, wherein X ₅ is -COX ₁₀ and X ₁₀ is a substituted or unsubstituted phenyl group, 2-furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2 -pyridyl group, 3pyridyl group, 4-pyridyl group, C 1 -C 8 alkyl group, C ₂ -C ₈ alkenyl group or C ₂ -C ₈ alkynyl group or X ₅ represents -COOOX _{| 0} and X ₁₀ represents substituted or unsubstituted C ₃ -C ₈ alkyl group, C ₂ -C ₈ alkenyl group or C ₂ -C ₈ alkynyl group. 135. The pharmaceutical composition of claim 133, characterized in that X ₅ is -COX ₁₀ and X ₁₀ is phenyl, or X ₅ is -COOX ₁₀ and _{X] 0} represents a tertiary butyl group. Pharmaceutical composition according to claim 129, characterized in that X ₃ represents a furyl or thienyl group, R ₇ represents an ethyl group and X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a tertiary butyl group. 137. Pharmaceutical composition according to claim 129, characterized in that X3 represents a substituted or unsubstituted furyl group, _R7a represents an ethyl group and X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 138. A pharmaceutical composition according to claim 129, wherein X ₃ represents a substituted or unsubstituted thienyl group, R _7a represents an ethyl group and X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 139. A pharmaceutical composition according to claim 129, wherein X ₃ represents an isobutenyl group, R _7a represents an ethyl group and X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 140. The pharmaceutical composition of claim 129, characterized in that X ₃ represents an alkyl group, R _7a is ethyl, and X ₅ is -COX ₁₀ and _{X] o} represents a phenyl group, or X ₅ is -COOX ₁₀ and X ₁₀ is tertiary butyl group. 141. A pharmaceutical composition according to claim 129, wherein X ₃ represents a 2-furyl or 2-thienyl group, R _1a represents an ethyl group, X ₅ represents COOX ₁₀ and X ₁₀ represents a tertiary butyl group. 142. A pharmaceutical composition according to claim 129, wherein X ₃ represents a 2-furyl group, R _7a represents an ethyl group, X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 143. A pharmaceutical composition according to claim 129, wherein X ₃ represents a 2-thienyl group, R _7a represents an ethyl group, X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 144. A pharmaceutical composition according to claim 129, wherein X ₃ represents an isobutenyl group, X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 145. The pharmaceutical composition of claim 129, wherein X ₃ represents a cycloalkyl group, X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. 146. An oral administration composition comprising a taxane according to claim 1 and at least one pharmaceutically acceptable carrier. 147. The composition of claim 146, 65219, characterized in that X ₃ represents a 2 furyl group, a 3-furyl group, a 2-thienyl group. 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C 1 -C ₈ alkyl group, C ₂ -C ₈ alkenyl group or C ₂ -C ₈ alkynyl group. 148. A composition according to claim 146, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a tertiary butyl group. Composition according to claim 146, characterized in that it is an ethyl or propyl group. A composition according to claim 149, wherein X ₃ represents a 2 furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3 pyridyl group, 4-pyridyl group, C ₂ - An C ₈ alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₂ -C ₈ alkynyl group. The composition of claim 150, wherein X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a tertiary butyl group. 152. The composition according to claim 150, characterized in that X ₃ is furyl, thienyl or isobutenyl, _{R? A} is ethyl, X ₅ is -COX ₁₀ wherein _{X] 0} represents a phenyl group, or X ₅ is -COOOX ₁₀ , where X ₁₀ represents a tertiary butyl group. Composition according to claim 146, characterized in that X ₃ represents an alkyl group, R 2 _a represents an ethyl group and X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a tertiary butyl group. A composition according to claim 152, wherein X ₃ represents a 2-furyl or 2-thienyl group, R _7a represents an ethyl group, X ₅ represents -COX ₁₀ and X ₁₀ represents a tert-butyl group or X ₅ represents -COX ₁₀ and X _{) O} represents a phenyl group. 155. A composition according to claim 154, wherein X ₃ represents a 2 furyl group, R _7a represents an ethyl group, X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group. 156. A composition according to claim 154, wherein X ₃ represents a 2-thienyl group, R _7a represents an ethyl group, X ₅ represents -COOOX _{) O} and X ₁₀ represents a tertiary butyl group. 157. A composition according to claim 152, wherein X ₃ represents an isobutyl group, R _7a represents an ethyl group and X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COOOX ₁₀ and X ₁₀ represents tertiary butyl group. 158. A composition according to claim 157, wherein X ₃ represents an isobutenyl group, R _1a represents an ethyl group, X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. Composition according to claim 152, characterized in that X ₃ represents a phenyl group, R _7a represents an ethyl group, X ₅ represents -COOOX ₁₀ and X ₁₀ represents a tertiary butyl group. Use of the taxane according to claim 1 for the preparation of a pharmaceutical composition for oral administration to inhibit tumor growth in mammals. Use according to claim 160, characterized in that X ₃ represents a 2 furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C-C an alkyl group, a C 1 -C alkenyl group or a C ₂ C ₈ alkynyl group. Use according to claim 161, characterized in that X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a tertiary butyl group. Use according to claim 160, wherein R _7a represents an ethyl or propyl group. Use according to claim 163, characterized in that X ₃ represents a 2 furyl group, 3-furyl group, 2-thienyl group, 3-thienyl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, C-C an alkyl group, a C ₂ -C ₈ alkenyl group, or a C ₈ alkynyl group. Use according to claim 164, wherein X ₃ represents _-COX10 and _X10 is phenyl, or X ₅ is _-COOX10 and _X10 is t-butyl. Use according to claim 160, characterized in that X ₃ represents a furyl group, a thienyl or isobutene group, R _7a represents an ethyl group, X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group, or X ₅ represents -COX _{] 0} and X ₁₀ represent a tertiary butyl group. Use according to claim 166, characterized in that X ₃ represents an alkyl group, R _7a represents an ethyl group, X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group, or X ₅ represents -COX ₁₀ and X ₁₀ represents tertiary butyl group. Use according to claim 166, characterized in that X ₃ represents a 2-furyl or 2-thienyl group, R _7a represents an ethyl group, X ₅ represents -COX ₁₀ and X ₁₀ represents a tert-butyl group or X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group. Use according to claim 168, characterized in that X ₃ represents a 2 furyl group, R _7a represents an ethyl group, X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group. Use according to claim 166, characterized in that X ₃ represents a 2-thienyl group, R _1a represents an ethyl group, X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group. Use according to claim 166, characterized in that X ₃ represents an isobutynyl group, R _7a represents an ethyl group, X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group, or X ₅ represents -COOOX _{] 0} and X ₁₀ represents tertiary butyl group. 172. The method of claim 171 wherein _X3 is isobutenyl, R _7a is ethyl, X ₅ is -COOX ₁₀ and X _1o represents a tertiary butyl group. 173. Use of a taxane according to claim 92 for the preparation of a pharmaceutical composition for oral administration for inhibiting tumor growth in mammals. Use according to claim 173, characterized in that X ₃ represents a phenyl group, isobutenyl group, furyl or thienyl group, R _7a represents ethyl group, X ₅ represents -COX ₁₀ and X ₁₀ represents a phenyl group or X ₅ represents - CoOX ₁₀ and X ₁₀ is a tertiary butyl group. 175. A pharmaceutical composition comprising a taxane according to claim 92 and at least one pharmaceutically acceptable carrier. 176. A pharmaceutical composition comprising a taxane according to claim 96 and at least one pharmaceutically acceptable carrier.